Miracle-dz/UniFAR-FTUs huggingface dataset:
Adherence to Adjuvant Hormonal Therapy and Its Relationship to Breast Cancer Recurrence and Survival Among Low-income Women

Objectives:Although clinical trials have demonstrated the benefit of adjuvant hormonal therapy for hormone receptor-positive breast cancer, it is not known whether poor medication adherence might impact outcomes, particularly in the context of a low-income population traditionally underrepresented in clinical trials. We explored the relationship between adherence to tamoxifen or selective aromatase inhibitors with cancer recurrence and death in a low-income, Medicaid-insured population. Methods:Using a Medicaid claims-tumor registry and National Death Index data, we evaluated adherence to adjuvant hormonal therapy [defined by the medication possession ratio (MPR)], cancer recurrence, and cancer-specific survival for female breast cancer diagnosed from 1998 to 2002, in North Carolina. Multivariate Cox proportional hazards models and logistic regression models were used to examine the role of adherence on cancer recurrence and survival. Results:The sample consisted of 857 cases, mean age 67.7 years, 56.9% white, 60.9% local stage, with a mean follow-up of 4.4 years. Mean first-year MPR was 77%. MPR adherence was not significantly associated with cancer-related death [adjusted hazards ratio=1.18 (95% confidence interval, 0.54-2.59)], or recurrence [adjusted odds ratio=1.49 (95% confidence interval, 0.78-2.84)]. There was also no significant interaction between adherence and use of concurrent CYP2D6 enzyme inhibitors. Discussion:Hormonal therapy adherence was not associated with breast cancer outcomes in this low-income population with relatively poor adherence. Although suboptimal adherence is considered to be an important clinical problem, its effects on breast cancer outcomes may be masked by patient genetic profiles, tumor characteristics, and behavioral factors.
Artesunate induces apoptosis via a Bak‐mediated caspase‐independent intrinsic pathway in human lung adenocarcinoma cells

This report is designed to explore the exact molecular mechanism by which artesunate (ART), a semisynthetic derivative of the herbal antimalaria drug artemisinin, induces apoptosis in human lung adenocarcinoma (ASTC‐a‐1 and A549) cell lines. ART treatment induced ROS‐mediated apoptosis in a concentration‐ and time‐dependent fashion accompanying the loss of mitochondrial potential and subsequent release of Smac and AIF indicative of intrinsic apoptosis pathway. Blockage of casapse‐8 and ‐9 did not show any inhibitory effect on the ART‐induced apoptosis, but which was remarkably prevented by silencing AIF. Of the utmost importance, ART treatment induced the activation of Bak but not Bax, and silencing Bak but not Bax remarkably inhibited ART‐induced apoptosis and AIF release. Furthermore, although ART treatment did not induced a significant down‐regulation of voltage‐dependent anion channel 2 (VDAC2) expression and up‐regulation of Bim expression, silencing VDAC2 potently enhanced the ART‐induced Bak activation and apoptosis which were significantly prevented by silencing Bim. Collectively, our data firstly demonstrate that ART induces Bak‐mediated caspase‐independent intrinsic apoptosis in which Bim and VDAC2 as well as AIF play important roles in both ASTC‐a‐1 and A549 cell lines, indicating a potential therapeutic effect of ART for lung cancer. J. Cell. Physiol. 227: 3778–3786, 2012. © 2012 Wiley Periodicals, Inc.
An Outcome-Based Action Study on Changes in Fitness, Blood Lipids, and Exercise Adherence, Using the Disconnected Values (Intervention) Model

The authors' purpose in this action study was to examine the effect of a 10-week intervention, using the Disconnected Values Model (DVM), on changes in selected measures of fitness, blood lipids, and exercise adherence among 51 university faculty (10 men and 41 women) from a school in the southeastern United States. The DVM is an intervention model that is intended to provide incentive to replace unhealthy with healthy behavioral patterns. Multivariate Mixed Model analyses indicated significantly improved fitness (ie, cardiovascular, strength, percent body fat) and lipid profile (eg, blood cholesterol, triglycerides) scores between pre- and postintervention on all measures (ps < .05) with the exception of blood pressure and high-density lipoprotein cholesterol (ps > .05). Adherence for cardiovascular activity averaged 22 out of 30 sessions (73%), and strength-training adherence averaged 13 out of 20 sessions (65%). The results of this outcome-based study suggest that the DVM provides an effective cognitive-behavioral approach to promoting regular exercise.
Activation of NFAT-Dependent Gene Expression by Nef: Conservation among Divergent Nef Alleles, Dependence on SH3 Binding and Membrane Association, and Cooperation with Protein Kinase C-θ

ABSTRACT Here we show that the potential to regulate NFAT is a conserved property of different Nef alleles and that Nef residues involved in membrane targeting and SH3 binding are critical for this function. Cotransfection of an activated protein kinase C-θ (PKC-θ) with Nef implicated PKC-θ as a possible physiological cofactor of Nef in promoting NFAT-dependent gene expression and T-cell activation.
Relationship of hepatitis C virus infection with diabetes in the U.S. population

An association of hepatitis C virus (HCV) infection with diabetes has been reported in many studies, but few have been population based and applied standard criteria for diabetes diagnosis. We examined this relationship using recent population‐based data from the U.S. National Health and Nutrition Examination Survey. Adult participants (15,128) in the 1999‐2010 surveys had data on diabetes status and serum HCV antibody (anti‐HCV) or HCV RNA. Using American Diabetes Association criteria, diabetes was defined as a health care provider diagnosis, serum hemoglobin A1C (A1C) ≥6.5%, or fasting plasma glucose (FPG) ≥126 mg/dL, prediabetes as A1C 5.7%‐<6.5% or FPG 100‐<126 mg/dL, and normal glucose as A1C <5.7% and FPG <100 mg/dL. Odds ratios (ORs) for diabetes and prediabetes, comparing persons with HCV infection to those without, were adjusted for demographics, BMI, C‐reactive protein, smoking, drinking, and blood transfusion before 1992. Among participants without diabetes, we compared mean insulin resistance (IR), estimated using homeostasis model assessment (HOMA‐IR), by HCV status. The overall prevalence of anti‐HCV+ was 1.7%, of HCV RNA+ 1.1%, of diabetes 10.5%, and of prediabetes 32.8%. The prevalence of diabetes and prediabetes did not differ by HCV status. In multivariate‐adjusted analysis, diabetes remained unassociated with anti‐HCV (OR, 1.0; 95% confidence interval [CI]: 0.6‐1.7) or with HCV RNA (OR, 1.1; 95% CI: 0.6‐1.9). In contrast, elevated alanine aminotransferase and gamma glutamyltransferase activities were associated with diabetes regardless of HCV status. HOMA‐IR was not associated with HCV markers in unadjusted or multivariate‐adjusted analyses (P > 0.05). Conclusion: In the U.S. population, HCV was not associated with diabetes or with IR among persons with normal glucose. Previously reported relationships of HCV with diabetes were possibly attributable to the effect of elevated liver enzymes. (Hepatology 2014;60:1139–1149)
Long‐term survival of 458 young breast cancer patients

The authors report the long‐term survival of 458 young breast cancer patients with follow‐up times ranging from 20 to 51 years. Patients with distant metastases at diagnosis were not included in the study. An excess breast cancer mortality was observed for at least 40 years after diagnosis. At 40 years, the actuarial breast cancer survival for all patients was 32% ± 3% (standard error). For patients with localized and regional disease, it was 53% ± 6% and 19% ± 3%, respectively. A persistent excess mortality after 40 years, however, could not be ruled out because too few patients remained at risk. It is concluded that a cured fraction of patients defined as a group subject only to normal mortality risks, in practice, can only be identified in young patients with a low expected mortality, since older patients give only minor contributions to long‐term survival results. In an unselected series of breast cancer patients, an excess breast cancer mortality will probably persist during a period that is longer than the life expectancy of the average patient. A parametric survival model, the log‐normal model, was found to provide a good fit to the observed survival data. The cured fraction of patients predicted by the model was similar to the actuarial breast cancer survival at 40 years. These results suggest that the model could be used as a tool for analyzing observed survival patterns in breast cancer. It might thus provide an alternative to the conventional 5‐ or 10‐year rates. The good fit of the model also suggests that late recurrences represent one end of a continuous, broad spectrum of behavior in disseminated breast cancer.
Protective autoimmunity: interferon‐γ enables microglia to remove glutamate without evoking inflammatory mediators

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia that repopulate the lesion site are the usual suspects for causing redox imbalance and inflammation and thus further exacerbating the neurotoxicity. However, our group recently demonstrated that early post‐injury activation of microglia as antigen‐presenting cells correlates with an ability to withstand injurious conditions. Moreover, we found that T cells reactive to CNS‐specific self‐antigens protected neurons against glutamate toxicity. Here, we show that antigen‐specific autoimmune T cells, by tailoring the microglial phenotype, can increase the ability of microglia‐enriched cultures to remove glutamate. This T‐cell‐mediated effect could not be achieved by the potent microglia‐activating agent lipopolysaccharide (LPS), but was dose‐dependently reproduced by the Th1 cytokine interferon (IFN)‐γ and significantly reduced by neutralizing anti‐IFN‐γ antibodies. Under the same conditions, IFN‐γ had no effect on cultured astrocytes. Up‐regulation of glutamate uptake induced by IFN‐γ activation was not accompanied by the acute inflammatory response seen in LPS‐activated cultures. These findings suggest that T cells or their cytokines can cause microglia to adopt a phenotype that facilitates rather than impairs glutamate clearance, possibly contributing to restoration of homeostasis.
Translating uveal melanoma cytogenetics into clinical care.

OBJECTIVE To report our experience in translating uveal melanoma cytogenetics to routine clinical practice. METHODS In 1998, we confirmed that monosomy 3 in uveal melanomas correlates with mortality. In 1999, we started offering all patients treated by enucleation or local resection the possibility of monosomy 3 testing, using fluorescence in situ hybridization. In 2006, we started analyzing tumors with multiplex ligation-dependent probe amplification, which provided more information from smaller samples. In 2007, we extended this service to patients undergoing radiotherapy or phototherapy. RESULTS Initial expectations regarding the sensitivity and specificity of monosomy 3 tests in predicting metastatic death were found to be overoptimistic. Cytogenetic classification of uveal melanomas into "lethal" and "nonlethal" types was insufficient for estimating risk of metastasis. Prognostication also required consideration of (1) clinical tumor stage; (2) histologic grading of malignancy; and (3) influence of age and sex on life expectancy. We developed a neural network for such multivariate analysis. Metastatic deaths occurred without monosomy 3, possibly because small deletions were missed or because of tumor heterogeneity. CONCLUSION Genomic typing of uveal melanomas proved more complex than we had anticipated but enabled us to reassure patients with a good prognosis while targeting systemic screening at high-risk cases.
Nursing Diagnosis in Patients with Liver Cirrhosis in Use of Feeding Tube

The objective was to identify the most frequent nursing diagnoses labels in patients with liver cirrhosis in use of feeding tube. A descriptive research was carried out in a Brazilian Hospital with 20 adult patients. Systematic data collection utilized the Conceptual Model of Wanda Horta, the first nurse to introduce the concept of Nursing Process in Brazil. The six phases of the nursing diagnostic reasoning proposed by Risner were used; nursing diagnoses were described according to NANDA-I taxonomy II. Patients were mainly male; half of them were middle age adults; they had an average of 12.8 nursing diagnoses labels; and the most frequent were: risk for aspiration and risk for infection. Nurses needed to develop effective skills to properly diagnose in order to provide safe care and improve patient outcomes.
Biological Cumulative Learning through Intrinsic Motivations: A Simulated Robotic Study on the Development of Visually-Guided Reaching

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PHYLOGENETIC ANALYSIS OF CHLOROPLAST DNA RESTRICTION SITE DATA AT HIGHER TAXONOMIC LEVELS: AN EXAMPLE FROM THE ASTERACEAE

Chloroplast DNA variation was examined among 57 genera of Asteraceae representing 15 currently recognized tribes. Complete cleavage maps were constructed for 11 six‐base pair restriction enzymes, and a total of 927 cleavage site differences was detected, 328 of which are phylogenetically informative. The data were used to construct phylogenetic trees using both Wagner and Dollo parsimony and the resulting monophyletic groups were evaluated statistically using the bootstrap method. The level of homoplasy in the restriction site data is 54–56% (excluding autapomorphies), most of which is due to parallel site losses. The most parsimonious trees generated by both parsimony methods have nearly identical topologies at lower taxonomic levels, but differ in subfamilial circumscriptions and tribal groupings. Dollo parsimony provides support for the monophyly of two subfamilies, the Lactucoideae (excluding the Barnadesiinae) and Asteroideae, but Wagner parsimony supports the monophyly of the Asteroideae only. This incongruence is due to different assumptions of the two parsimony methods about relative rates of parallel site gains and losses. After eliminating the six most rapidly changing restriction sites or performing successive approximation, Wagner parsimony produces trees with the same subfamilial groupings as the Dollo trees. We conclude that the Dollo tree with two monophyletic subfamilies is the best estimate of phylogenetic relationships in the Asteraceae because this method more accurately reflects the evolution of restriction sites. We also demonstrate that in spite of high levels of homoplasy in chloroplast DNA restriction site data at these higher taxonomic levels, it is possible to make statistically supported estimates of phylogenetic relationships.
A proteomics approach to survey the antigenicity of the influenza virus by mass spectrometry

A proteomics‐based approach is described that combines gel electrophoresis and MS in order to identify protein interactions and the nature of the interaction interface with high‐sample throughput and sensitivity. Results for protein antigens of the influenza virus have demonstrated that the approach can be successfully employed to detect determinants within the hemagglutinin antigen of two divergent type A forms of the virus in present circulation. The determinants are localised to residues 206–224 following tryptic digestion of the hemagglutinin antigen. Specific peptide–antibody complexes formed after treatment of gel‐recovered antigen are shown to be able to be preserved on the MALDI target array as has been previously demonstrated in this laboratory for whole virus. The approach has broad applicability for the analysis of a wide array of protein complexes with identification of the interaction interface in a single step with high‐sample throughput and at low sample levels.
Inversion polymorphism in a two-locus genetic system.

The types of equilibria possible with an inversion in a two-locus system are considered, and their stability properties investigated. With complete suppression of crossing-over in inversion heterozygotes, there are three possible types of stable equilibria; which of these is reached by a new inversion depends on the fitness effects of the two loci concerned. With one of these equilibria, basically involving cumulative overdominance of the selected loci, the inverted and standard sequences are genetically homogeneous and differ with respect to both loci. With the other types of equilibrium, the standard sequence remains heterogeneous for one or both loci. It is shown that this situation may lead to variations in karyotypic fitnesses when the inversion is changing in frequency. It is also found that, with certain fitness relationships, two alternative stable equilibria may coexist; the final frequency reached by an inversion may therefore depend on the population's history. The effects of double crossing-over in inversion heterozygotes were also investigated, and it was shown that the equilibria with double crossing-over are closely related to the corresponding equilibria without it, except that both sequences are more heterogeneous genetically. Within each sequence there is almost complete linkage equilibrium between the selected loci, although both are in linkage disequilibrium with the inversion itself. It was also found that, with double crossing-over, the population tends to remain for many thousands of generations in a state of quasi-equilibrium. In this state, the inversion tends not to return to its original frequency after a perturbation; also, it may remain for a long time relatively homogeneous genetically, especially when rare. These results were compared with those from experiments and observations on inversion polymorphisms.
A Theoretical Model for the Associative Nature of Conference Participation

Participation in conferences is an important part of every scientific career. Conferences provide an opportunity for a fast dissemination of latest results, discussion and exchange of ideas, and broadening of scientists’ collaboration network. The decision to participate in a conference depends on several factors like the location, cost, popularity of keynote speakers, and the scientist’s association with the community. Here we discuss and formulate the problem of discovering how a scientist’s previous participation affects her/his future participations in the same conference series. We develop a stochastic model to examine scientists’ participation patterns in conferences and compare our model with data from six conferences across various scientific fields and communities. Our model shows that the probability for a scientist to participate in a given conference series strongly depends on the balance between the number of participations and non-participations during his/her early connections with the community. An active participation in a conference series strengthens the scientist’s association with that particular conference community and thus increases the probability of future participations.
Whose Culture Matters? Near-Market Knowledge and Its Impact on Foreign Market Entry Timing

Market entry decisions are some of a firm's most important strategic choices. Although some recent studies have begun to consider the impact of learning and experience on foreign market entry, no study has examined the impact of a firm's own operations in similar markets on subsequent entry decisions. In this study, the authors introduce the concept of near-market knowledge to reflect the knowledge firms generate by operating in markets that are culturally and economically similar. The authors compile extensive data on the complete foreign market entries of 19 multinational firms. They use a hazard model on 722 entry observations to evaluate the impact of the dynamic near-market knowledge measures and other economic and cultural variables on foreign market entry timing. In contrast with much previous research, the authors find that cultural distance from the domestic market is not a significant factor. However, the authors find significant effects for the new measures of near-market cultural and economic knowledge and for several other economic variables as well. The authors discuss the implications of these findings for further research and management practice.
Dendritic nicotinic receptors modulate backpropagating action potentials and long‐term plasticity of interneurons

Stratum radiatum interneurons, unlike pyramidal cells, are rich in nicotinic acetylcholine receptors (nAChRs); however, the role of these receptors in plasticity has remained elusive. As opposed to previous physiological studies, we found that functional α7‐subunit‐containing nAChRs (α7‐nAChRs) are abundant on interneuron dendrites of rats. Moreover, dendritic Ca2+ transients induced by activation of α7‐nAChRs increase as a function of distance from soma. The activation of these extrasynaptic α7‐nAChRs by cholinergic agonists either facilitated or depressed backpropagating action potentials, depending on the timing of α7‐nAChR activation. We have previously shown that dendritic α7‐nAChRs are involved in the regulation of synaptic transmission, suggesting that α7‐nAChRs may play an important role in the regulation of the spike timing‐dependent plasticity. Here we provide evidence that long‐term potentiation is indeed boosted by stimulation of dendritic α7‐nAChRs. Our results suggest a new mechanism for a cholinergic switch in memory encoding and retrieval.
Tuberculosis in Saudi Arabia: prevalence and antimicrobial resistance

Abstract Tuberculosis is a serious contagious disease caused by Mycobacterium tuberculosis and is endemic in many countries. Over the past two decades, there has been an increase in the number of multidrug-resistant TB and extensively drug-resistant TB cases around the world. As in many countries, TB is common in Saudi Arabia. The disease is particularly relevant in the Kingdom because of its population dynamics including a large number of resident expatriates mainly from TB endemic regions and the influx of millions of pilgrims to the country each year during the Hajj and Umrah seasons. This review investigates the prevalence and antimicrobial resistance among M. tuberculosis isolates from Saudi Arabia, highlighting the variations in rates in different geographical areas with particularly high rates in the main cities and regions hosting the annual pilgrimage. The review also refers to the measures needed to prevent and control TB transmission in the country.