Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of MDR1 methylation on the curative effect of interventional embolism chemotherapy for cervical cancer

Background Multi-drug resistance (MDR) is the main cause of tumor failure to chemotherapy. This study aims to explore the influence of MDR1 methylation on curative effect of interventional embolism chemotherapy for cervical cancer. Methods Sixty-seven patients with cervical cancer receiving embolism chemotherapy were selected, and 45 normal cervical tissues were included as a control. Immunohistochemistry was used to detect the level of P-glycoprotein (P-gp) in cervical cancer, and to make an analysis compared with normal tissues. The methylation status of the MDR1 gene promoter region 16 CpG units was analyzed by using kilobase-specific cracking and matrix-assisted laser desorption ionization time of flight mass spectrometry. Results The results indicated that the positive expression rates of P-gp were 0% (0/45) in normal cervical tissue, and 61.19% (41/67) and 77.61% (52/67) before and after interventional embolism chemotherapy in cervical cancer tissues, respectively. There were significant differences compared with normal cervical tissues (χ2=4.2523, 0.0392). The positive expression rate of P-gp before chemotherapy was negatively correlated with efficacy of chemotherapy (r=−0.340, P=0.005). Methylation rate of 13 CpG units in normal tissues was significantly greater than cervical tissues (P<0.05). In cervical cancer tissue, methylation rate of six CpG units before interventional embolism chemotherapy was higher than after chemotherapy, but that of one CpG unit was lower than after chemotherapy (P<0.05). The methylation rate of one CpG unit with effective chemotherapy before chemotherapy was significantly higher than ineffective chemotherapy (P<0.05), and the other CpG units were similar (P>0.05). Conclusion P-gp expression level coded by MDR1, methylation status of partial MDR1 gene promoter regions CpG island, is closely related to the efficacy of interventional embolism chemotherapy for cervical cancer before the operation.
Quality of follow-up after hospitalization for mental illness among patients from racial-ethnic minority groups.

OBJECTIVE Outpatient follow-up after hospitalization for mental health reasons is an important indicator of quality of health systems. Differences among racial-ethnic minority groups in the quality of service use during this period are understudied. This study assessed the quality of outpatient treatment episodes following inpatient psychiatric treatment among blacks, whites, and Latinos in the United States. METHODS The Medical Expenditure Panel Survey (2004-2010) was used to identify adults with any inpatient psychiatric treatment (N=339). Logistic regression models were used to estimate predictors of any outpatient follow-up or the beginning of adequate outpatient follow-up within seven or 30 days following discharge. Predicted disparities were calculated after adjustment for clinical need variables but not for socioeconomic characteristics, consistent with the Institute of Medicine definition of health care disparities as differences that are unrelated to clinical appropriateness, need, or patient preference. RESULTS Rates of follow-up were generally low, particularly rates of adequate treatment (<26%). Outpatient treatment prior to inpatient care was a strong predictor of all measures of follow-up. After adjustment for need and socioeconomic status, the analyses showed that blacks were less likely than whites to receive any treatment or begin adequate follow-up within 30 days of discharge. CONCLUSIONS Poor integration of follow-up treatment in the continuum of psychiatric care leaves many individuals, particularly blacks, with poor-quality treatment. Culturally appropriate interventions that link individuals in inpatient settings to outpatient follow-up are needed to reduce racial-ethnic disparities in outpatient mental health treatment following acute treatment.
Associations of smoking with overall obesity, and central obesity: a cross-sectional study from the Korea National Health and Nutrition Examination Survey (2010-2013)

OBJECTIVES: The association between smoking and obesity is a significant public health concern. Both are preventable risk factors of cardiovascular disease and a range of other conditions. However, despite numerous previous studies, no consensus has emerged regarding the effect of smoking on obesity. We therefore carried out a novel study evaluating the relationship between smoking and obesity. METHODS: A total of 5,254 subjects aged 19 years or older drawn from the 2010-2013 Korea National Health and Nutrition Examination Survey were included in this cross-sectional study. Smoking was examined both in terms of smoking status and the quantity of cigarettes smoked by current smokers. Multiple logistic regression analysis was used to assess the association between smoking and obesity. Overall obesity was defined as a body mass index (BMI) ≥25 kg/m2, and central obesity was defined as a waist circumference ≥90 cm for males and ≥85 cm for females. We adjusted for the possible confounding effects of age, sex, physical activity, alcohol consumption, and the presence of hypertension or diabetes. RESULTS: A statistically significant difference in central obesity according to smoking status was identified. Current smokers were more likely to be centrally obese than never-smokers (adjusted odds ratio,1.30; 95% confidence interval, 1.02 to 1.67). However, no significant association was found between smoking and obesity defined by BMI. Moreover, among current smokers, no statistically significant association was found between the daily amount of smoking and obesity or central obesity. CONCLUSIONS: Smoking was positively associated with central obesity. Current smokers should be acquainted that they may be more prone to central obesity.
Relative Concentration of Cry1A in Maize Leaves and Cotton Bolls with Diverse Chlorophyll Content and Corresponding Larval Development of Fall Armyworm (Lepidoptera: Noctuidae) and Southwestern Corn Borer (Lepidoptera: Crambidae) on Maize Whorl Leaf Profiles

Abstract To manage insect resistance to transgenic crops that express insecticidal proteins from Bacillus thuringiensis (Bt) Berliner, the U.S. Environmental Protection Agency recommends a refuge-based insect resistance management strategy where a percentage of non-Bt (refuge) crop is grown in proximity to a Bt-expressing crop. An important requirement for this strategy is that the toxin exists at a high effective dose for control of the target pest(s), so that heterozygous individuals in the population do not reach adulthood. Factors that cause reduced levels of toxin in the plant are a threat to this strategy. We quantified Cry1Ab from different areas of the maize, Zea mays L. , leaf. In general, the distal tip of the V7 maize leaf had a higher concentration of Cry1Ab compared with the middle section of the V7 leaf, and the middle section of the developing V9 leaf had the lowest concentration of Cry1Ab. When these sections of maize tissue were fed to fall armyworm, Spodoptera frugiperda (J.E. Smith), and southwestern corn borer, Diatraea grandiosella Dyar, there was not a reduction in development or an increase in mortality with tissue that had higher concentrations of toxin. Another study tested the relative concentration of Cry1Ab between the white-yellow, yellow-green, and green portions of the developing ninth leaf within the maize whorl. There were differences in Cry1Ab concentration among these leaf areas. The green tissue had the highest concentration of toxin followed by the yellow-green and white-yellow tissues. Correlations between concentration of Cry1Ab and 5-d fall armyworm larval weights among the three leaf color profiles were all significant and negative, i.e., decreased concentration of Cry1Ab in the leaf tissue resulted in increased 5-d larval weights. There was 100% mortality to the southwestern corn borer larvae fed Cry1Ab maize leaf tissue. Differences in the amount of Cry1Ab in the developing V9 leaf profiles did not alter the absolute susceptibility of the southwestern corn borer to the toxin. In cotton, Gossypium hirsutum L. , the amount of Cry1Ac was significantly lower in boll tips where flowers had remained attached compared with normal boll tips. Boll tips where the flowers remained attached are often the site where corn earworms, Helicoverpa zea (Boddie), penetrate Bt cotton bolls. This study demonstrated that, in two diverse plant species, tissue that has low chlorophyll content does not fully express Cry1A. Photosynthesis regulating factors related to mRNA transcription and translation should be studied for their effect on Cry1A production and insect control.
Gender Differences in Extreme Mathematical Achievement: An International Perspective on Biological and Social Factors1

Genetic and other biological explanations have reemerged in recent scholarship on the underrepresentation of women in mathematics and the sciences. This study engages this debate by using international data—including math achievement scores from the Third International Mathematics and Sciences Study and country‐level data from the World Bank, the United Nations, the International Labour Organization, the World Values Survey, and the International Social Survey Programme—to demonstrate the importance of social factors and to estimate an upper bound for the impact of genetic factors. The author argues that international variation provides a valuable opportunity to present simple and powerful arguments for the continued importance of social factors. In addition, where previous research has, by and large, focused on differences in population means, this work examines gender differences throughout the distribution. The article shows that there is considerable variation in gender differences internationally, a finding not easily explained by strictly biological theories. Modeling the cross‐national variation in gender differences with country‐level predictors reveals that differences among high achievers are related to gender inequality in the labor market and differences in the overall status of men and women.
Early-Life Overweight Trajectory and CKD in the 1946 British Birth Cohort Study

Background Few studies have examined the impact of childhood obesity on later kidney disease, and consequently, our understanding is very limited. Study Design Longitudinal population-based cohort. Setting & Participants The Medical Research Council National Survey of Health and Development, a socially stratified sample of 5,362 singletons born in 1 week in March 1946 in England, Scotland, and Wales, of which 4,340 were analyzed. Predictor Early-life overweight latent classes (never, prepubertal only, pubertal onset, or always), derived from repeated measurements of body mass index between ages 2 and 20 years. Outcomes & Measurements The primary outcome was chronic kidney disease (CKD), defined as creatinine- or cystatin C–based estimated glomerular filtration rate (eGFRcr and eGFRcys, respectively) <60 mL/min/1.73 m2 or urine albumin-creatinine ratio (UACR) ≥3.5 mg/mmol measured at age 60-64 years. Associations were explored through regression analysis, with adjustment for socioeconomic position, smoking, physical activity level, diabetes, hypertension, and overweight at ages 36 and 53 years. Results 2.3% of study participants had eGFRcr <60 mL/min/1.73 m2, 1.7% had eGFRcys <60 mL/min/1.73 m2, and 2.9% had UACR ≥3.5 mg/mmol. Relative to being in the never-overweight latent class, being in the pubertal-onset– or always-overweight latent classes was associated with eGFRcys-defined CKD (OR, 2.04; 95% CI, 1.09-3.82). Associations with CKD defined by eGFRcr (OR, 1.27; 95% CI, 0.71-2.29) and UACR (OR, 1.33; 95% CI, 0.70-2.54) were less marked, but in the same direction. Adjustment for lifestyle and health factors had little impact on effect estimates. Limitations A low prevalence of CKD resulted in low statistical power. No documentation of chronicity for outcomes. All-white study population restricts generalizability. Conclusions Being overweight in early life was found to be associated with eGFRcys-defined CKD in later life. The associations with CKD defined by eGFRcr and UACR were less marked, but in the same direction. Reducing or preventing overweight in the early years of life may significantly reduce the burden of CKD in the population.
The inverted U curve and emergency medicine: Overdiagnosis and the law of unintended consequences

We all think and assume that more is better, but unintended consequences can arise in a complex system. However, in our complex world, everything of consequence follows an inverted U curve. The inverted U curve helps us challenge our natural assumption that more is better. This leads us to the issue of overdiagnosis and the harms that result. Journals are now publishing lists of studies where more medical care caused harm. Changing diagnostic thresholds together with the fear of uncertainty by both patients and doctors has a synergistic and costly effect on the health system. The over‐reliance on technology tends to supplant clinical judgement. This intervention bias promotes the overutilisation of diagnostic testing. What patients actually value is thinking doctors who talk to them. Promoting clinical judgement reinforces the mantra that less is more, resulting in positively intended consequences. This essay aims to be a thought‐provoking commentary of our practice.
The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats.

Previous animal studies have indicated that drugs targeted at metabotropic glutamate (mGlu) receptors may be useful for treatment of psychosis. In this article, the effects of the novel, potent, and selective mGlu2/3 receptor agonists LY354740 and LY379268, and the clinically effective agents clozapine and haloperidol, were investigated using phencyclidine (PCP; 5 mg/kg)- versus d-amphetamine (AMP; 3 mg/kg)-evoked motor activities. LY354740 (1-10 mg/kg s.c.), LY379268 (0.3-3 mg/kg s.c.), clozapine (1-10 mg/kg s.c.), and haloperidol (0.03-1 mg/kg s.c.) reversed the increases in ambulations, fine motor (nonambulatory) movements, and decreased time at rest evoked by PCP. Furthermore, the inhibitions of the PCP response by the mGlu2/3 agonist LY379268, but not by clozapine, were completely reversed by the selective mGlu2/3 receptor antagonist LY341495. Doses of LY354740 and LY379268 that blocked the effects on PCP had no effects on rotorod performance, and (with the exception of rearing behavior) had minimal effects on AMP-evoked motor activities. Clozapine blocked AMP-induced rearing but enhanced AMP-induced ambulations and fine movements at the lower doses (1 and 3 mg/kg). Unlike the mGlu2/3 agonists, the highest dose of clozapine tested (10 mg/kg) impaired animals on the rotorod. Haloperidol potently blocked all PCP and AMP effects, but only at doses associated with motor impairment. These data demonstrate that mGlu2/3 receptor agonists act via a unique mechanism to selectively block PCP-induced behaviors. Moreover, the marked mGlu2/3 receptor-mediated inhibitions of PCP-evoked behaviors by LY354740 and LY379268, with minimal effects on AMP, may indicate potential antipsychotic effects in humans in the absence of dopamine mediated extrapyramidal side effects.
Genetic consequences of habitat fragmentation and restoration

Title of Document: GENETIC CONSEQUENCES OF HABITAT FRAGMENTATION AND RESTORATION. Michael Warren Lloyd, Doctor of Philosophy, 2012 Directed By: Associate Professor, Maile C. Neel, Department of Plant Science and Landscape Architecture & Department of Entomology The objective my dissertation was to assess the effects of habitat loss and fragmentation on genetic diversity and landscape connectivity. I focused on Vallisneria americana Michx. (Hydrocharitaceae), a submersed aquatic plant species found in the Chesapeake Bay. Vallisneria americana has undergone dramatic changes in abundance and distribution throughout its range and has been targeted for restoration, which makes it ideal for examining the effects habitat loss and fragmentation. I examined the naturally occurring genetic diversity across the Chesape ake Bay and its major tributaries. Sites were genetically diverse, but had a ran ge of genotypic diversities. There were four genetic regions, corresponding with geographic reg ions in the Bay. Vallisneria americana has been the target of restoration, and restoration techniques could be influencing genetic diversity and potentially lowering overall success. I examined various restoration techniques across eight restoration s ites, and found that technique did not greatly influence genetic diversity. However, sm all population size, significant inbreeding coefficients, and low overlap of allele composition among sites provide cause for concern. Measures of functional and potential connectivity provide insights into the degree of contemporary gene flow occurring across a landscape. Pollen disper sal distance was measured using indirect paternity analysis, and is spatiall y restricted to only a few meters. Dispersal at this scale imposes small genetic ne ighborhoods within sites, evidenced by high seed relatedness within mothers. I used a graph theoretic approach to examine the distribution and potential connectivity of histori c and current patches of V. americana. There was a high turnover in the distribution of patches, and connectivity varied through time, but even if all habitat were occupied, increases in overall network connectivity would not necessarily be observed. I developed an individual based model that I used to test the ability of measures of genetic differentiation to detect changes in landscape connectivity. Genet ic differentiation measures became significant after two generations, but the magnitude of change in each was small in all cases and extremely small when populati on sizes are greater than 100 individuals. These results suggest that genetic differ entiation measures alone are inadequate to rapidly detect changes in connectivity. GENETIC CONSEQUENCES OF HABITAT FRAGMENTATION AND RESTORATION.
Neurotrophin and Neurotrophin Receptor Expression in Alveolar Macrophages: An Immunocytochemical Study

Abstract Alveolar macrophages play a crucial role in regulating lung immune responses and in maintaining the integrity of the respiratory tract. Neurotrophins (NTs), besides to their neurotrophic activities, exhibit physiological effects in the immune system. In this study, nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), NT-3 and low- (p75) and high affinity (Trks) NT receptors were investigated by immunocytochemistry in cytospin centrifuged preparations of human alveolar macrophages. Approximately 2.5% alveolar macrophages were immunoreactive for NGF, whereas no macrophages displaying immunoreactivity for BDNF or NT-3 were observed. A 3.5% macrophages displayed immunoreactivity for TrkA-receptor protein, 10% for TrkB-receptor protein (full length isoform), and 2% for TrkC-receptor protein. No low-affinity p75 NT and TrkB[-] truncated isoform receptor immunoreactive macrophages were found. These findings support the hypothesis that NTs and the corresponding receptors may play a role in regulating immunological and functional activity of alveolar macrophages via paracrine/autocrine mechanisms.
Immunity to Recombinant Plasmodium falciparum Merozoite Surface Protein 1 (MSP1): Protection in Aotus nancymai Monkeys Strongly Correlates with Anti-MSP1 Antibody Titer and In Vitro Parasite-Inhibitory Activity

ABSTRACT A number of malarial blood-stage candidate vaccines are currently being tested in human clinical trials, but our understanding of the relationship between clinical immunity and data obtained from in vitro assays remains inadequate. An in vitro assay which could reliably predict protective immunity in vivo would facilitate vaccine development. Merozoite surface protein1 (MSP1) is a leading blood-stage malaria vaccine candidate, and anti-MSP1 antibodies from individuals that are clinically immune to malaria inhibit the invasion of Plasmodium merozoites into erythrocytes in vitro. Using expression in Escherichia coli and subsequent refolding, we have produced two allelic forms of MSP142 (FVO and 3D7). Aotus nancymai monkeys were immunized with MSP142-FVO, MSP142-3D7, or a combination of FVO and 3D7 allelic forms, (MSP142-C1) and were subsequently challenged with Plasmodium falciparum FVO parasites. Sera obtained prior to challenge were tested by standardized enzyme-linked immunosorbent assay (ELISA) to determine antibody titer, and immunoglobulin G (IgG) fractions were also obtained from the same sera; the IgG fractions were tested in an in vitro growth inhibition (GI) assay to evaluate biological activity of the antibodies. Regardless of the immunogen used, all monkeys that had >200,000 ELISA units against MSP142-FVO antigen before challenge controlled their infections. By contrast, all monkeys whose purified IgGs gave <60% inhibition activity in an in vitro GI assay with P. falciparum FVO required treatment for high parasitemia after challenge. There is a strong correlation between ELISA units (Spearman rank correlation of greater than 0.75) or GI activity (Spearman rank correlation of greater than 0.70) and protective immunity judged by various parameters (e.g., cumulative parasitemia or day of patency). These data indicate that, in this monkey model, the ELISA and GI assay values can significantly predict protective immunity induced by a blood-stage vaccine, and they support the use of these assays as part of evaluation of human clinical trials of MSP1-based vaccines.
Prognosis of Pulmonary Embolism with Right Ventricular Dysfunction

Background: Mortality rate of pulmonary embolism (PE) at 3 months is over 15% for the high risk presentation and varies from 3% to 15% for the intermediate-risk presentation. Thrombolysis in intermediate-risk PE remains a matter of debate. Methods: We undertook a retrospective study over a 11-year period including patients with high and intermediatehigh- risk PE, hospitalised in a medical ICU in a University hospital, to assess medium and long-term prognosis. Results: Our series involved 145 patients, of whom 63 presented high risk PE and 82 had an intermediate-highrisk PE. Thirty-six patients (24.8%) died in the intensive care unit (ICU) including high-risk PE: 34/63 (53.9%), of whom 25 after inaugural cardiac arrest (CA); intermediate-high-risk PE: 2/82 (2.4%). On multivariate analysis, high blood lactates (OR: 1.88; IC 95% 1.18-3.02, p=0.0083), resuscitated CA (OR: 12.33; IC 95% 1.1-137.4, p=0.041), low subaortic velocity time integral (VTI) (OR: 9.22, IC 0.38-0.81, p=0.0024) were independent factors of in-ICU mortality. Twenty-seven patients died after ICU discharge. Echocardiographic checks were performed in 63 patients, in which 4 (6.3%) presented a chronic thromboembolic pulmonary hypertension (CTPH). Conclusion: High-risk PE still has a high mortality rate in the ICU especially when revealed by a cardiac arrest. High blood lactates, resuscitated CA, and low subaortic VTI were independent predictive factors of mortality. In our retrospective cohort, long-term prognosis was good with only 4 cases of CTPH. The low mortality observed with anticoagulant-only treatment do not encourage thrombolysis for management of intermediate-high-risk PE patients.