Miracle-dz/UniFAR-FTUs huggingface dataset:
Celecoxib enhanced the sensitivity of cancer cells to anticancer drugs by inhibition of the expression of P‐glycoprotein through a COX‐2‐Independent Manner

The P‐glycoprotein (p170, P‐gp) encoded by human MDR1 gene functions as a pump to extrude anticancer drugs from cancer cells. Over‐expression of p170 is closely related to primary and induced drug resistance phenotype of tumor cells. Recent studies have demonstrated that expression of cyclooxygenase‐2 (COX‐2) is positively correlated with the p170 level, suggesting a potential of COX‐2 specific inhibitors in regulation of cytotoxicity of anticancer agents. Celecoxib is one of the specific inhibitors of COX‐2 and has been widely used in clinic. However, its function in the response of cancer cells to anticancer drugs and the related mechanism are still waiting to be investigated. To explore the correlation of celecoxib and the p170‐mediated drug resistance, the role of celecoxib in drug response of cancer cells was analyzed with flow cytometry, high performance liquid chromatography (HPLC), and colony formation experiments. Celecoxib (50 µM) was found to significantly enhance the sensitivity of MCF‐7 and JAR/VP16 cells to tamoxifen and etoposide, respectively, by inhibition of p170 expression and increase in intracellular accumulation of the drugs. However, celecoxib did not affect pump function of p170. Enzyme activity and methylation analyses demonstrated that the inhibitory effect of celecoxib on p170 was independent on COX‐2 but closely related to hypermethylation of MDR1 gene promoter. Our study suggested that celecoxib was a potential agent for enhancement of the sensitivity of cancer cells to anticancer drugs. It also provided a links between epigenetic change of MDR1 and drug response of cancer cells. J. Cell. Biochem. 108: 181–194, 2009. © 2009 Wiley‐Liss, Inc.
Electronic properties, hydrogen bonding, stacking, and cation binding of DNA and RNA bases

This review summarizes results concerning molecular interactions of nucleic acid bases as revealed by advanced ab initio quantum chemical (QM) calculations published in last few years. We first explain advantages and limitations of modern QM calculations of nucleobases and provide a brief history of this still rather new field. Then we provide an overview of key electronic properties of standard and selected modified nucleobases, such as their charge distributions, dipole moments, polarizabilities, proton affinities, tautomeric equilibria, and amino group hybridization. Then we continue with hydrogen bonding of nucleobases, by analyzing energetics of standard base pairs, mismatched base pairs, thio‐base pairs, and others. After this, the nature of aromatic stacking interactions is explained. Also, nonclassical interactions in nucleic acids such as interstrand bifurcated hydrogen bonds, interstrand close amino group contacts, C—H … O interbase contacts, sugar–base stacking, intrinsically nonplanar base pairs, out‐of‐plane hydrogen bonds, and amino–acceptor interactions are commented on. Finally, we overview recent calculations on interactions between nucleic acid bases and metal cations. These studies deal with effects of cation binding on the strength of base pairs, analysis of specific differences among cations, such as the difference between zinc and magnesium, the influence of metalation on protonation and tautomeric equlibria of bases, and cation–π interactions involving nucleobases. In this review, we do not provide methodological details, as these can be found in our preceding reviews. The interrelation between advanced QM approaches and classical molecular dynamics simulations is briefly discussed. © 2002 Wiley Periodicals, Inc. Biopoly (Nucleic Acid Sci) 61: 3–31, 2002; DOI 10.1002/bip.10048
HTLV‐I viral escape and host genetic changes in the development of adult T cell leukemia

In the pathogenesis of adult T cell leukemia (ATL), an oncogenetic role of the human T cell lymphotropic virus type I (HTLV‐I) Tax protein, viral escape from the host immune system, and host genetic changes have been proposed as contributory factors. We examined the premature stop codons in tax gene as one of the mutations that may lead to escape of HTLV‐I from the cytotoxic T lymphocyte (CTL) response in HTLV‐I carriers, to test whether a putative CTL escape mutant can emerge in the early stage of ATL development and whether HTLV‐I infected cells with such a mutation can proliferate subsequently. We also examined deletion of cyclin‐dependent kinase inhibitor 4 (INK4) genes and mutation of p53 gene in combination with changes in the HTLV‐I genome in acute type ATL to test whether host genetic changes promoted the malignant transformation of ATL cells that carry putative CTL escape mutations. The premature stop codon in tax gene existed in many non‐ATL HTLV‐I carriers as a minor population but not in the commonest HTLV‐I sequence of the individual. This minor population with a premature stop codon did not expand subsequently in 3 asymptomatic carriers tested. There were cases who had a mutation or deletion in HTLV‐I who also have either deletion of INK4 genes or mutation in p53 gene. Our findings suggest that CTL escape mutation can occur at an early stage of ATL development, and that certain host genetic changes favor the development of the aggressive form of ATL. © 2005 Wiley‐Liss, Inc.
Understanding same-sex male and female partners’ restrained eating in the context of their relationships

This study examined weight status and dietary restraint among same-sex couples using Actor–Partner Interdependence Models. Body mass indices and restrained eating behaviors (i.e., cognitive dietary restraint, uncontrolled eating, and emotional eating) were assessed for members of 144 same-sex couples (72 lesbian and 72 gay couples; mean age = 33.74 years, standard deviation = 11.27 years). Results indicated that both men and women who were relatively heavy and who had relatively thin partners were at particular risk of engaging in restrained eating. These findings extend our understanding of partner comparison processes within the context of same-sex relationships in determining men and women’s eating behaviors.
Polymorphism of age‐related changes in interleukin (IL) production: differential changes of T helper subpopulations, synthesizing IL 2, IL3 and IL4

Inbred mice were examined for strain differences in age‐associated changes in the capacity to synthesize interleukin (IL), i.e. IL2, IL3 and IL4 after stimulation with phorbol myristate acetate (PMA) and calcium ionophore (A23187). Production of IL2remains constant in A/J, DBA/1 and DBA/2 mice and decreases with age in one of the strains examined (C57BL/6J). Strain differences in age‐associated changeof synthesis did not show the relation between youthful synthetic capacity and magnitude of later decrease (“economic correction”) which is observed in several other systems. This difference between different types of polymorphisms is attributed to an age‐associated defect in intrinsic capacity to synthesize IL2 which may occur in onlyone of the tested strains, C57BL/6J. In contrast to IL 2 production, the quantities of IL3 and IL4 increase progressively, with advancing age, in mice of the three strains tested. T cells from old mice contain a greater frequency of cells producing IL3, than do those of young mice. In addition, synthesis of IL3 is induced at a relatively lower concentration of PMA in cells from old animals and this may be a consequence of different signal requirements of the two subsets of the T helper cells, but also a change in intrinsic properties of these cells. Since IL3 and IL4 production, but not IL2 production, increaseswith age, it is reasonable to conclude that this reflects an expansion of a T helper cellpopulation which secretes IL3 and IL4, but not IL2, presumably TH2.
Emergency Department Management of Community-Acquired Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus is a known cause of a variety of illnesses that present to the emergency department, including skin and soft tissue infections, pneumonia, and sepsis. Managing these conditions has become more difficult with the emergence of bacterial strains in the community that are resistant to traditional first-line antibiotics. Emergency care providers need to be aware of the increased prevalence of these resistant bacteria, to understand the characteristics of the infections with which they are associated, and to know the effective antibiotic options for treating these bacterial infections in the emergency department patient population.
Primary Nonadherence, Associated Clinical Outcomes, and Health Care Resource Use Among Patients with Rheumatoid Arthritis Prescribed Treatment with Injectable Biologic Disease-Modifying Antirheumatic Drugs

BACKGROUND: Adherence to biologic disease-modifying antirheumatic drugs (bDMARDs) among patients with rheumatoid arthritis (RA) is often suboptimal in routine clinical practice. Low or nonadherence can reduce the effectiveness of bDMARD therapies. OBJECTIVE: To evaluate filling of newly prescribed initial bDMARDs for the treatment of RA and evaluate potential for characterizing treatment decisions and patient outcomes. METHODS: In this retrospective cohort analysis, patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM code 714.xx) were selected from a de-identified database of clinical information from the Electronic Health Record (EHR; Humedica) database linked to health care claims (Optum) from commercial and Medicare Advantage health plans (2007-2013). The first biologic prescription date in EHR was the index date. Patients were categorized as filling the prescription within 30 days (early fillers), 31-180 days (late fillers), or not at all within 180 days (nonfillers) of index date. RESULTS: Of 373 patients meeting inclusion criteria, 170 (45.6%), 59 (15.8%), and 144 (38.6%) were categorized as early fillers, late fillers, and nonfillers, respectively. Most prescriptions were written or ordered for tumor necrosis factor inhibitors (88.7%). Compared with late and nonfillers, early fillers were younger and more likely to be female, with higher pain scores (among those reporting pain scores) and RA severity scores pre-index, and filled more prescriptions for any reason pre-index. More nonfillers (66.0%) were Medicare patients than early (17.7%) and late (35.6%) fillers. During days 0-30 post-index, conventional synthetic DMARD use was greatest for early fillers (45.9%) and lowest among nonfillers (24.3%); however, during days 31-180 post-index, the proportion was highest for late fillers (61.0%) and lowest for nonfillers (35.4%). Of early fillers, 12.9% did not fill/receive a bDMARD after 30 days. Only 23 patients had pre/post-index pain scores, and 47 patients had a rationale for stopping or not filling a bDMARD. In patients with pharmacy and medical coverage for 180 days post-index, early fillers had greater RA-related pharmacy and medical resource use and costs than late and nonfillers combined. CONCLUSIONS: These findings confirm a high rate of primary nonadherence to bDMARDs among patients with RA.
Liability of the Voltage-Gated Sodium Channel Gene SCN2A R19K Polymorphism to Oxaliplatin-Induced Peripheral Neuropathy

Aim: It was the aim of this study to test the hypothesis that the voltage-gated sodium channel gene SCN2A R19K polymorphism confers liability to oxaliplatin-induced peripheral neuropathy (OXLIPN). Methods: Sixty-two patients with advanced colorectal cancer were genotyped, using allele-specific primers and SYBR green in real-time polymerase chain reaction. All patients had received adjuvant oxalipla-tin-based chemotherapy. The severity of OXLIPN was defined by means of the clinical total neuropathy score. Following the discontinuation of treatment, 36/62 patients (58.1%) developed OXLIPN. Grade I neurotoxicity was revealed in 14 (38.9%) patients and grade II neurotoxicity in 22 (61.1%) patients. Results: From patients without OXLIPN (n = 26), 80.8% (n = 21) were homozygous for G, 19.2% (n = 5) were heterozygous (AG) and none was homozygous for A. The corresponding percentages for patients developing any grade of OXLIPN (n = 36) were similar. Likewise, among patients experiencing OXLIPN, insignificant differences in R19K genotypes were revealed between those with grade I versus grade II neurotoxicity. Conclusion: Our study failed to provide evidence to support a causal relationship between the SCN2A R19K polymorphism and OXLIPN.
Developing Positive Emotion through Affective Design for Interactive Information Seeking

This research aims to convert the negative human emotional state to positive emotional state for better decision making in information seeking. A psychological emotional model will be used to identify the type of emotions. As emotions are triggers of decision making process in human and emotions are being influenced by the design of information seeking systems and the information overload, human behavior in information seeking is diverted to the negative emotional states due to design and information overload. Prior research has been focusing on specific type of emotion such as stress, frustration, anxiety in different scenarios. However, the gap is still there to not just only measure the type of emotion but to improve the affective wellbeing condition using the emotional data through improving the search system design. Design can heal or hurt. We would like to transform human negative emotional state to positive well-being by a better design approach in both human-computer interaction and human-human interaction.
Assessment of Venous Thromboembolism Prophylaxis in Neurological Patients with Restricted Mobility - VTE-NEURO Study.

ABSTRACT The authors present the data of a medical registry which evaluated if the physicians assess VTE risk in stroke patients, during hospitalization period and at hospital discharge and if the thromboprophylaxis is used according to National Guidelines for VTE Prophylaxis. 884 patients with acute ischemic stroke patients were enrolled between June 2010 and December 2011, from 62 centers, 51.4% male and 48.6% female with mean age 70.07 years (68.25 years in the male group and 71.92 years in the female one). There were two co-primary endpoints: the percentage of patients at risk for VTE at hospital admission assessed by the physician, and the percentage of patients with risk factors for VTE that persist at hospital discharge from the total number of patients hospitalized with ischemic stroke. The secondary endpoints were: the percentage of hospitalized patients receiving prophylaxis according to the National Guidelines of VTE Prophylaxis from the total number of patients at risk of VTE, the percentage of hospitalized patients with VTE risk receiving recommendation for thromboprophylaxis at discharge, the duration and the type of VTE prophylaxis in hospitalized patients, the duration and the type of VTE prophylaxis at discharge. RESULTS 879 (99.4%) of the total number of patients at risk of VTE have received prophylaxis during hospitalization. The most frequently types of prophylaxis used during hospitalisation were LMWH in 96.3% of the patients and mechanic method in 16.6% that were in accordance with the National Guidelines of VTE Prophylaxis recommendations. CONCLUSIONS There is a clear improvement in both assessment and thromprophylaxis recommendation in acute stroke patients with restricted mobility at VTE risk and in our country. LMWH is preferred to unfractionated heparin for venous thromboembolism prophylaxis in this high-risk patient population in view of its better clinical benefits to risk ratio and convenience of once daily administration.
A Biomechanical Investigation of Vertebroplasty in Osteoporotic Compression Fractures and in Prophylactic Vertebral Reinforcement

Study Design. Cadaveric single vertebrae were used to evaluate vertebroplasty as a prophylactic treatment and as an intervention for vertebral compression fractures. Objective. To investigate the biomechanical characteristics of prophylactic reinforcement and postfracture augmentation of cadaveric vertebrae. Summary of Background Data. Percutaneous vertebroplasty is a treatment option for osteoporotic vertebral compression fractures. Short-term results are promising, but longer-term studies have suggested a possible accelerated failure rate in the adjacent vertebral body. Limited research has been conducted into the effects of prophylactic vertebroplasty in osteoporotic vertebrae. This study aims to elucidate the biomechanical differences between the 2 treatment groups. Methods. Human vertebrae were assigned to 2 scenarios: Scenario 1 simulated a wedge fracture followed by cement augmentation; Scenario 2 involved prophylactic augmentation using vertebroplasty. Micro-CT imaging was performed to assess the bone mineral density, vertebral dimensions, fracture pattern, and cement volume. All augmented specimens were then compressed under an eccentric flexion load to failure. Results. Product of bone mineral density and endplate surface area gave a good prediction of failure strength when compared with actual failure strength of specimens in Scenario 1. Augmented vertebral bodies showed an average cement fill of 23.9% ± 8.07%. There was a significant postvertebroplasty increase in failure strength by a factor of 1.72 and 1.38 in Scenarios 1 and 2, respectively. There was a significant reduction in stiffness following augmentation for Scenario 1 (t = 3.5, P = 0.005). Stiffness of the vertebral body in Scenario 2 was significantly greater than observed in Scenario 1 (t = 4.4, P = 0.0002). Conclusion. Results suggest that augmentation of the vertebrae postfracture significantly increases failure load, while stiffness is not restored. Prophylactic augmentation was seen to increase failure strength in comparison to the predicted failure load. Stiffness appears to be maintained suggesting that prophylactic vertebroplasty maintains stiffness better than vertebroplasty postfracture.
Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) Program

Health‐compromising behaviors among survivors of childhood cancer may increase their risks of cancer recurrence and the onset of chronic disease in adulthood. Regardless of whether such behaviors occur singly or in combination with one another, multiple behavioral risk factors must be identified and addressed early to promote better health outcomes within this special population. Adolescent survivors may be especially vulnerable, as reported rates of smoking and other risky behaviors are at or near levels of their healthy peers. The psychological literature suggests stress may play a role in risk behavior initiation and maintenance, including multiple behavioral risks, and that adolescent survivors are stress‐prone. This report focuses on the prevalence and co‐occurrence of three behavioral risk factors (cigarette use, insufficient physical activity, and non‐adherence to sun protection recommendations) and describes stress‐health behavior relationships in this special population.
Human cytomegalovirus (HCMV) immediate-early enhancer/promoter specificity during embryogenesis defines target tissues of congenital HCMV infection

Congenital human cytomegalovirus (HCMV) infection is a common cause of deafness and neurological disabilities. Many aspects of this prenatal infection, including which cell types are infected and how infection proceeds, are poorly understood. Transcription of HCMV immediate-early (IE) genes is required for expression of all other HCMV genes and is dependent on host cell transcription factors. Cell type-specific differences in levels of IE transcription are believed to underlie differences in infection permissivity. However, DNA transfection experiments have paradoxically suggested that the HCMV major IE enhancer/promoter is a broadly active transcriptional element with little cell type specificity. In contrast, we show here that expression of a lacZ gene driven by the HCMV major IE enhancer/promoter -524 to +13 segment is restricted in transgenic mouse embryos to sites that correlate with known sites of congenital HCMV infection in human fetuses. This finding suggests that the IE enhancer/promoter is a major determinant of HCMV infection sites in humans and that transcription factors responsible for its regulation are cell type-specifically conserved between humans and mice. The lacZ expression patterns of these transgenic embryos yield insight into congenital HCMV pathogenesis by providing a spatiotemporal map of the sets of vascular, neural, and epithelial cells that are likely targets of infection. These transgenic mice may constitute a useful model system for investigating IE enhancer/promoter regulation in vivo and for identifying factors that modulate active and latent HCMV infections in humans.
Determinants of Discretionary Fair Value Measurements: The Case of Level 3 Assets in the Banking Sector

The objective of our research was to respond to the call of Barth and Taylor () for more research to examine the role of discretion in fair value estimates. Specifically, we investigate factors that explain banksâ€™ accounting choices to use Level 3 valuation inputs from the fair value measurement hierarchy. Using handâ€ collected data from a sample of international banks during 2009â€“2013, we find that incentives to use discretionary Level 3 valuation inputs, which can provide an opportunity to manage earnings, are associated with both firmâ€ level and countryâ€ level determinants. Additional tests provide evidence that Level 3 â€˜transferâ€ inâ€™ behaviour is related to changes in bank characteristics.
Obesity and Obstructive Sleep Apnea in Patients With Keratoconus in a Turkish Population

Purpose: The aim of this study was to compare the frequency of occurrence of obesity and high risk of developing obstructive sleep apnea (OSA) in a keratoconus population with that of a control group. Methods: This prospective, case-controlled multicenter study was performed on patients with keratoconus and age- and gender-matched control subjects. One hundred forty-six patients were included in each group, and the Berlin Questionnaire was used for classifying patients as having a high risk or low risk of developing OSA. The patients' demographic and clinical characteristics were compared with the Mann–Whitney U test for continuous variables and with the &khgr;2 test for categorical variables. Results: The keratoconus (85 male/61 female) and control (79 male/67 female) groups' median ages were 25 (8–65) and 24 (9–60) years, respectively. Of the 146 patients in each group, 11 (7.5%) patients were determined to be at a high risk of developing OSA in the keratoconus group, and 8 (5.5%) patients were determined to be at a high risk of developing OSA in the control group. There was no significant difference between the groups (P = 0.477). The keratoconus and control groups' median body mass index values were found to be within normal ranges of 23.2 and 23.4, respectively. Conclusions: In this study, the mean body mass index value of the keratoconus group was determined to be within normal limits. In a Turkish population, the ratio of a high risk of developing OSA was not found to be significantly different between the keratoconus and control groups.