Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality of care and outcomes of adults with asthma treated by specialists and generalists in managed care.

BACKGROUND The growth of managed health care in the United States has been accompanied by controls on access to specialty physician services. We examined the relationship of physician specialty to treatment and outcomes of patients with asthma in managed care plans. METHODS We conducted a mail survey of adult asthma patients who were enrolled in 12 managed care organizations and had at least 2 contacts for asthma (International Classification of Diseases, Ninth Revision, Clinical Modification code 493.x) during the previous 24 months; we also surveyed their treating physicians. This report concerns 1954 patients and their 1078 corresponding physicians. Treatment indicators included use of corticosteroid inhalers, use of peak flow meters, allergy evaluation, discussion of triggers, and patient self-management knowledge. Outcome measures included canceled activities, hospitalization or emergency department visits, asthma attacks, workdays lost, asthma symptoms, physical and mental health, overall satisfaction with asthma care, and satisfaction with communication with physicians and nurses. RESULTS Significant differences were noted for patients of specialists and experienced generalists compared with those of generalist physicians. Peak flow meter possession was reported by 41.9% of patients of generalists, 51.7% of patients of experienced generalists, and 53.8% of patients of pulmonologists or allergists. Compared with patients of generalists, outcomes were significantly better for patients of allergists with regard to canceled activities, hospitalizations and emergency department visits for asthma, quality of care ratings, and physical functioning. Patients of pulmonologists were more likely to rate improvement in symptoms as very good or excellent. CONCLUSIONS In a managed health care setting, physicians' specialty training and self-reported expertise in treating asthma were related to better patient-reported care and outcomes.
The variegated role of the state in different gated neighbourhoods in China

Housing commodification has led to the development of gated neighbourhoods in China. However, the types of gated neighbourhoods are very different from each other, and include ‘commodity housing’, affordable housing and resettlement housing. They might not be the same as the commonly known ‘gated communities’, which are characterised by both gating and private governance. Using three cases in the city of Wenzhou, we analyse the motivations for development, service provision and property management, and neighbourhood control. In commodity housing, the state is still visible and self-governance is limited, while the real estate developer leads land development and property management. In affordable housing, the state regulates the standards and the prices of services, while the developer is the provider of these services. In resettlement housing, the state uses a state-owned enterprise to relocate households, while the homeowners’ association and the service charges are ineffective. All these cases demonstrate the important and variegated role of the state and provide a more nuanced understanding of these gated neighbourhoods.
Evaluation of liposomal curcumin cytochrome p450 metabolism.

BACKGROUND Curcumin (diferuloylmethane) is a commonly used spice and nutritional supplement that has demonstrated potential anti-tumor and anti-inflammatory activity. There is limited information regarding curcumin metabolism and the potential for drug-drug interactions. The objective of this study was to characterize the hepatic metabolism of synthetic curcumin used in the liposomal curcumin formulation. MATERIALS AND METHODS High-throughput cytochrome P450 (CYP450) metabolism inhibition assays were conducted in vitro evaluating CYP450 3A4, 2C8, 2C9, and 2D6. An ex vivo model of cryopreserved human hepatocytes was used to evaluate the CYP450 metabolism induction potential of curcumin for CYP P450 3A4, 2C8/2C9, and 2D6. RESULTS In the in vitro CYP450 inhibition studies, curcumin at any concentration did not inhibit CYP450 3A4 or CYP450 2D6 activity. At a curcumin concentration of 58.3 microM, 10.5% and 22.5% inhibition of CYP450 2C9 and CYP450 2C8 activity, respectively, was observed. In the ex vivo hepatocyte inductions studies, minimal to no induction of CYP450 3A4, CYP450 2C8/2C9 or CYP450 2D6 was observed. Rifampicin did not induce the metabolism of curcumin and curcumin did not induce its own metabolism. CONCLUSION There is low potential for CYP450 mediated drug interactions at physiologic serum concentrations of liposomal curcumin. Based on preliminary data, liposomal curcumin will not interact with other chemotherapy agents that are metabolized and/or eliminated via the primary drug metabolizing CYP450 pathways.
BİLEŞİK ÖNCÜ GÖSTERGELER İLE BORSA İSTANBUL SEKTÖR ENDEKSLERİ ARASINDAKİ İLİŞKİNİN İNCELENMESİ

Ekonomik faaliyetlerde yasanabilecek dalgalanmalar tum piyasalari oldugu gibi hisse senedi piyasalarini da etkilemektedir. Bilesik oncu gostergeler ise ekonomiye iliskin beklentileri ortaya koymaktadir. Bu calismada 2006:01-2016:10 donemi icin bilesik oncu gostergeler endeksi ile 12 borsa sektor endeksi getirileri arasinda iliski olup olmadigi test edilmistir. Esbutunlesme iliskisi degiskenler farkli seviyede duragan olduklarindan Sinir Testi ile arastirilmistir. Yapilan analizler sonucunda bilesik oncu gostergeler ile calismada yer alan tum sektor endeksleri arasinda uzun ve kisa donemde iliski oldugu belirlenmistir. Ilaveten bilesik oncu gostergelerdeki artisin tum sektor endekslerini kisa donemde olumlu yonde etkiledigi tespit edilmistir. Nedensellik sonuclari ise cogunlukla bilesik oncu gostergelerin endekslerin nedeni oldugunu ortaya koymustur.
The antiviral compound enviroxime targets the 3A coding region of rhinovirus and poliovirus

Enviroxime is an antiviral compound that inhibits the replication of rhinoviruses and enteroviruses. We have explored the mechanism of action of enviroxime by using poliovirus type 1 and human rhinovirus type 14 as model systems. By varying the time of drug addition to virus-infected cells, we determined that enviroxime could be added several hours postinfection without significant loss of inhibition. This suggested that the drug targeted a step involved in RNA replication or protein processing. To identify this target, we mapped 23 independent mutations in mutants that could multiply in the presence of 1 microgram of enviroxime per ml. Each of these mutants contained a single nucleotide substitution that altered one amino acid in the 3A coding region. Using oligonucleotide-directed mutagenesis of cDNA clones, we have confirmed that these single-amino-acid substitutions are sufficient to confer the resistance phenotype. In addition, we conducted two experiments to support the hypothesis that enviroxime inhibits a 3A function. First, we determined by dot blot analysis of RNA from poliovirus-infected cells that enviroxime preferentially inhibits synthesis of the viral plus strand. Second, we demonstrated that enviroxime inhibits the initiation of plus-strand RNA synthesis as measured by the addition of [32P]uridine to 3AB in poliovirus crude replication complexes. To our knowledge, this is the first evidence that 3A can be targeted by antiviral drugs. We anticipate that enviroxime will be a useful tool for investigating the natural function of the 3A protein.
Original Contribution Prospective Study of Restless Legs Syndrome and Risk of Depression in Women

Most research on the association between restless legs syndrome (RLS) and depression has involved crosssectional data. The objective of the present study was to evaluate this issue prospectively among Nurses’ Health Study participants. A total of 56,399 women (mean age = 68 years) who were free of depression symptoms at baseline (2002) were followed until 2008. Physician-diagnosed RLS was self-reported. During 300,155 personyears of follow-up, the authors identified 1,268 incident cases of clinical depression (regular use of antidepressant medication and physician-diagnosed depression). Women with RLS at baseline were more likely to develop clinical depression (multivariate-adjusted relative risk (RR) = 1.5, 95% confidence interval (CI): 1.1, 2.1; P = 0.02) than those without RLS. The presence of RLS at baseline was also associated with higher scores on the 10item Center for Epidemiologic Studies Depression Scale (CESD-10) and the 15-item Geriatric Depression Scale (GDS-15) thereafter. Multivariable-adjusted mean differences were 1.00 (standard error, 0.12) for CESD-10 score and 0.47 (standard error, 0.07) for GDS-15 score between women with RLS and those without RLS (P < 0.0001). In conclusion, women with physician-diagnosed RLS had an increased risk of developing clinical depression and clinically relevant depression symptoms. Further prospective studies using refined approaches to ascertainment of RLS and depression are warranted.
E2A and HEB Are Required to Block Thymocyte Proliferation Prior to Pre-TCR Expression1

Thymocytes undergoing TCRβ gene rearrangements are maintained in a low or nonproliferating state during early T cell development. This block in cell cycle progression is not released until the expression of a functional pre-TCR, which is composed of a successfully rearranged TCRβ-chain and the Pre-Tα-chain. The regulatory molecules responsible for the coordination of these differentiation and proliferation events are currently unknown. E2A and HEB are structurally and functionally related basic helix-loop-helix transcription factors involved in T cell development. To reveal the function of E2A and HEB through the stage of pre-TCR expression and alleviate functional compensation between E2A and HEB, we use a double-conditional knockout model. The simultaneous deletion of E2A and HEB in developing thymocytes leads to a severe developmental block before pre-TCR expression and a dramatic reduction of Pre-Tα expression. These developmentally arrested thymocytes exhibit increased proliferation in vivo and dramatic expansion ex vivo in response to IL-7 signaling. These results suggest that E2A and HEB are not only critical for T cell differentiation but also necessary to retain developing thymocytes in cell cycle arrest before pre-TCR expression.
Culture in the rotating-wall vessel affects recombinant protein production capability of two insect cell lines in different manners

SummaryThe production of recombinant secreted alkaline phosphatase protein in virally infected insect cells was studied in shaker flask and high aspect rotating-wall vessel (HARV) culture. Two commonly used cell lines, Spodoptera frugiperda Sf-9 (Sf-9) and a nonaggregating isolate of the Trichoplusia ni BTI-Tn-5B1-4 (Tn-5B1-4) cell line, Trichoplusia ni Tn-5B1-4-NA (TN-5B1-4-NA), were used and monitored for 120-h postinfection. Different responses to culture in the HARV were seen in the two cell lines. While the Sf-9 cell line was able to produce slightly greater amounts of recombinant protein in the HARV than in shaker flask controls, the Tn-5B1-4-NA cell line produced significantly lesser amounts in the HARV than in the shaker flasks. Both cell lines exhibited longer life spans and longer periods of protein production in HARV culture than in shaker flask culture, presumably due to lower levels of shear encountered in the HARV. The important difference was in the protein production rate responses of the two cell lines. While the protein production rates of Sf-9 cells were comparable in both HARV and shaker flask cultures, the protein production rates of Tn-5B1-4-NA cells were much lower in HARV culture than in shaker flask cultures. The conclusion is drawn that cell line-specific adaptation to the HARV strongly influences recombinant protein production.
Possible Roles of CTGF/Hcs24 in the Initiation and Development of Ossification of the Posterior Longitudinal Ligament

Study Design. A biochemical and histochemical study investigating the role of CTGF/Hcs24 in the ossification of the posterior longitudinal ligament (OPLL) was conducted. Objective. To clarify the involvement of CTGF/Hcs24 in ectopic bone formation in OPLL through endochondral ossification using human tissue. Summary of Background Data. Previous studies have shown that various cytokines are involved in the occurrence or development of ectopic bone formation in OPLL. Recently, the authors cloned an mRNA predominantly expressed in chondrocytes by differential display PCR and found that its gene, hcs24, is identical to that of connective tissue growth factor. It has been shown that CTGF/Hcs24 plays a major role in endochondral ossification. Methods. Ossified ligament tissues were taken from seven male OPLL patients during surgery. Immunohistochemical staining was performed using an antibody specific for CTGF/Hcs24. Spinal ligament cells were isolated from five OPLL patients as well as five non-OPLL patients. The cells were incubated with recombinant human CTGF/Hcs24 or TGF&bgr;. The expression of ALP was analyzed by RT-PCR. For the effects of TGF&bgr;, the expression of CTGF/Hcs24 mRNA was analyzed. Results. Immunohistochemical staining showed that chondrocytes in the transitional region from nonossified to ossified ligament were stained with an antibody against CTGF/Hcs24. It was found that CTGF/Hcs24 enhanced the expression ALP mRNA in OPLL cells, whereas the expression remained unchanged in non-OPLL cells. The expression of CTGF/Hcs24 mRNA in OPLL and non-OPLL cell lines was increased by TGF&bgr;, and there was no significant difference between the two groups. However, TGF&bgr; and CTGF/Hcs24 enhanced the expression of ALP mRNA only in OPLL cells. Conclusions. According to the study results, CTGF/Hcs24 may not only be an important factor in the development of endochondral ossification in OPLL, but may also be responsible for initiating osteogenesis in spinal ligament cells.
Gene expression profiling by microarray analysis reveals an important role for caspase‐1 in dengue virus‐induced p53‐mediated apoptosis

Recently, a dengue virus‐induced apoptosis p53‐ and mitochondria‐mediated were reported in human and animal cells. To understand further the underlying mechanisms, a p53‐deficient cell line, H1299, and a p53‐knockin cell line, H273, were infected with dengue type 1 virus and the cellular gene expression profiles at the mRNA level were analyzed by affymetrix array analysis. The results showed 183 genes with at least twofold increase at mRNA expression level in dengue virus‐infected cells. Among the 183 genes, 68 genes were up‐regulated in both H1299 and H273 cells and 78 genes were found to be up‐regulated in only H273 cells. Eleven selected genes, mainly involved in IFN‐pathway, cell cycle, signal transduction, and ubiquitin–proteasome pathways were confirmed using qualitative and quantitative PCR. Interestingly, an approximately 32‐fold increase in caspase‐1 expression was observed in the p53‐knockin cell line, H273. Gene silencing of caspase‐1 or inhibition of caspase‐1 activity led to reduction in dengue virus‐induced apoptosis with minimal effect on virus replication. J. Med. Virol. 81:1069–1081, 2009. © 2009 Wiley‐Liss, Inc.
Dose-Rate Effects for Apoptosis and Micronucleus Formation in Gamma-Irradiated Human Lymphocytes

Abstract Boreham, D. R. , Dolling, J-A. , Maves, S. R. , Siwarungsun, N. and Mitchel, R. E. J. Dose-Rate Effects for Apoptosis and Micronucleus Formation in Gamma-Irradiated Human Lymphocytes. We have compared dose-rate effects for γ-radiation-induced apoptosis and micronucleus formation in human lymphocytes. Long-term assessment of individual radiation-induced apoptosis showed little intraindividual variation but significant interindividual variation. The effectiveness of radiation exposure to cause apoptosis or micronucleus formation was reduced by low-dose-rate exposures, but the reduction was apparent at different dose rates for these two end points. Micronucleus formation showed a dose-rate effect when the dose rate was lowered to 0.29 cGy/min, but there was no accompanying cell cycle delay. A further increase in the dose-rate effect was seen at 0.15 cGy/min, but was now accompanied by cell cycle delay. There was no dose-rate effect for the induction of apoptosis until the dose rate was reduced to 0.15 cGy/min, indicating that the mechanisms or signals for processing radiation-induced lesions for these two end points must be different at least in part. There appear to be two mechanisms that contribute to the dose-rate effect for micronucleus formation. One of these does not affect binucleate cell frequency and occurs at dose rates higher than that required to produce a dose-rate effect for apoptosis, and one affects binucleate cell frequency, induced only at the very low dose rate which coincidentally produces a dose-rate effect for apoptosis. Since the dose rate at which cells showed reduced apoptosis as well as a further reduction in micronucleus formation was very low, we conclude that the processing of the radiation-induced lesions that induce apoptosis, and some micronuclei, is very slow in quiescent and PHA-stimulated lymphocytes, respectively.
Analysis of cytogenetic alterations in stage III serous ovarian adenocarcinoma reveals a heterogeneous group regarding survival, surgical outcome, and substage

Ovarian cancer is the leading cause of death among patients with gynecological cancers, but the biology of these tumors is still among the least understood of all major human malignancies. In this study, comparative genomic hybridization was used to determine chromosomal alterations in 98 stage III serous papillary adenocarcinomas. The tumors were grouped according to survival and the main prognostic factors stage and surgical outcome. There were chromosomal imbalances that were significantly more common in tumors from patients who died than in tumors from patients who survived: gains of 1q24–qter and losses of 4p, 4q31.1–qter, 5q12–q22, 8p, 16q, and X. Furthermore, we observed that gains of 8q23–8q24.2 and losses of 4p, 4q13–4q26, 4q31.1–qter, 5q12–q22, 8p, and 16q were significantly more common in tumors from patients with macroscopic residual tumor after primary surgery, compared to tumors from those who had undergone radical surgery. Gains of 3q13.3–qter, 6p, 7q21–q31, and 11q13–q23 and losses of 4q31.1–qter and 16q were more common in stage IIIc tumors than in stage IIIa+b tumors. On the basis of our results, we suggest that there are biological differences among the groups mentioned above and that absence of chromosomal aberrations in specific regions predicts a good clinical outcome for individual patients. © 2004 Wiley‐Liss, Inc.
A conflict resolution model for sustainable heritage tourism

This paper uses Ajzen's theory of planned behavior (TPB) model to explain the formation of behavioral frameworks for conflict resolution. Using data about the Chengqi Earth building, UNESCO World Heritage Site, it puts forward an integrative TPB model with self‐regulation and social capital as a good fit to that data, which has better predictive power in relation to intentions than the original model. The results show that attitudes, subjective norms, perceived behavioral control, and self‐regulatory behavior positively affect intentions to seek conflict resolution. The paper concludes with insightful implications that can be applied to other areas of China and beyond.
Cytotoxic effect of accelerated carbon beams on glioblastoma cell lines with p53 mutation: clonogenic survival and cell-cycle analysis.

PURPOSE The cytotoxic effect of high-LET carbon beams was analysed on p53 mutant and wild-type glioblastoma cell lines. MATERIALS AND METHODS Three glioblastoma (U251MG, TK-1, A-172) cell lines, one medulloblastoma (ONS-76) and one fibroblast cell line (NB1RGB) were used. U251MG and TK-1 have mutated p53, A-172, ONS-76 and NB1RGB have wild-type p53. Gamma-ray and 290 MeV/u carbon mono-peak beams with average LET values of 20, 40, 81 and 105keV/microm were used. Cytotoxicity was measured by clonogenic survival assay and DNA histograms were analysed by flow cytometry. RESULTS The RBE values for carbon beams at D10 ranged from approximately 1.5-1.7 (20keV) to 2.9-3.1 (105keV). Although p53 mutants were more resistant than wild-types for all radiation qualities, carbon beams yielded a higher RBE in p53 mutants than in wild-types. Alpha values were significantly smaller in p53 mutants than wild-types for gamma- and 20 keV/microm radiations, while no significant difference was noticed for LET greater than 40 keV/microm. A G1 block was noticed after irradiation with gamma-rays and carbon beams of 20 and 40keV/microm in p53 wild-types. A more pronounced G2 block occurred in p53 mutants than wild-types in proportion to LET up to 105 keV/microm. CONCLUSION Accelerated carbon beams can yield higher RBE in gamma-resistant glioblastoma cell lines with p53 mutations. High-LET irradiation induces not only disappearance of the p53-dependent G1 block but also a greater G2 block in glioblastoma cell lines.
Expression of AeaHsp26 and AeaHsp83 in Aedes aegypti (Diptera: Culicidae) Larvae and Pupae in Response to Heat Shock Stress

ABSTRACT Immature mosquito development and survival of adults are highly sensitive to environmental temperature, which can alter gene expression during the mosquito life-cycle. To further understand how heat shock proteins are developmentally expressed in mosquitoes, we subjected first instar larvae, 16-h old pupae and female of Aedes aegypti (L.) (Diptera: Culicidae) to heat shock treatment for 0, 15, 30, 60, and 180 min at 23 and 42°C. The heat shock protein genes AeaHsp26, AeaHsp83, and AeaHsc70 were examined by comparing relative transcript expression levels at 42°C compared with 23°C. Upregulated transcripts from heat shock treatment at 42°C and control were further confirmed and quantified by quantitative real-time polymerase chain reaction. Data revealed that first instar larvae were more sensitive to heat shock treatment than pupae and adults (i.e., relative AeaHsp26 expression levels in larvae were 10-fold greater than in the females. AeaHsp83 expression levels in larvae, pupae and adults were upregulated 2- to 50-fold greater by heat shock treatment at 42°C compared with 23°C. AeaHsc70 expression levels in larvae, pupae and adults, however, were upregulated less than AeaHsp26 and AeaHsp83 at the higher temperature. Statistical analysis indicated that AeaHsp26 and AeaHsp83 genes were significantly upregulated in Ae. aegypti larvae and pupae after 15, 30, 60, and 180 min exposure to high temperature (42°C). The current study has shown that AeaHsp26 and AeaHsp83 are important markers of stress and may function as critical proteins to protect and enhance survival of Ae. aegypti larvae and pupae.