Miracle-dz/UniFAR-FTUs huggingface dataset:
Coverage and preventive screening.

CONTEXT Preventive care has been shown as a high-value health care service. Many employers now offer expanded coverage of preventive care to encourage utilization. OBJECTIVE To determine whether expanding coverage is an effective means to encourage utilization. DESIGN Comparison of screening rates before and after introduction of deductible-free coverage. SETTING People insured through large corporations between 2002 and 2006. PATIENTS OR OTHER PARTICIPANTS Preferred Provider Organization (PPO) enrollees from an employer introducing deductible-free coverage, and a control group enrolled in a PPO from a second employer with no policy change. MAIN OUTCOME MEASURES Adjusted probability of endoscopy, fecal occult blood test (FOBT), lipid screens, mammography, and Papanicolaou (pap) smears. INTERVENTION Introduction of first-dollar coverage (FDC) of preventive services in 2003. RESULTS After adjusting for demographics and secular trends, there were between 23 and 78 additional uses per 1,000 eligible patients of covered preventive screens (lipid screens, pap smears, mammograms, and FOBT), with no significant changes in the control group or in a service without FDC (endoscopy). CONCLUSIONS FDC improves utilization modestly among healthy individuals, particularly those in lower deductible plans. Compliance with guidelines can be encouraged by lowering out-of-pocket costs, but patients' predisposing characteristics merit attention.
The Effect of Coatings and Nerve Growth Factor on Attachment and Differentiation of Pheochromocytoma Cells

Cellular attachment plays a vital role in the differentiation of pheochromocytoma (PC12) cells. PC12 cells are noradrenergic clonal cells isolated from the adrenal medulla of Rattus norvegicus and studied extensively as they have the ability to differentiate into sympathetic neuron-like cells. The effect of several experimental parameters including (i) the concentration of nerve growth factor (NGF); (ii) substratum coatings, such as poly-L-lysine (PLL), fibronectin (Fn), and laminin (Lam); and (iii) double coatings composed of PLL/Lam and PLL/Fn on the differentiation process of PC12 cells were studied. Cell morphology was visualised using brightfield phase contrast microscopy, cellular metabolism and proliferation were quantified using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, and the neurite outgrowth and axonal generation of the PC12 cells were evaluated using wide field fluorescence microscopy. It was found that double coatings of PLL/Lam and PLL/Fn supported robust adhesion and a two-fold enhanced neurite outgrowth of PC12 cells when treated with 100 ng/mL of NGF while exhibiting stable metabolic activity, leading to the accelerated generation of axons.
Oral Administration of Transforming Growth Factor-β1 (TGF-β1) Protects the Immature Gut from Injury via Smad Protein-dependent Suppression of Epithelial Nuclear Factor κB (NF-κB) Signaling and Proinflammatory Cytokine Production*

Background: Intestinal production of TGF-β is decreased in neonatal necrotizing enterocolitis (NEC). Results: Oral administration of TGF-β (TGF-β1) inhibited inflammation in intestinal epithelium and systemic production of IL-6 and IFN-γ as well as NEC incidence in an animal model. Conclusion: Oral administration of TGF-β1 can compensate for TGF-β1 deficiency in gut diseases. Significance: TGF-β1 can potentially be used to prevent and treat gut diseases. Inflammatory immune responses play an important role in mucosal homeostasis and gut diseases. Nuclear factor κB (NF-κB), central to the proinflammatory cascade, is activated in necrotizing enterocolitis (NEC), a devastating condition of intestinal injury with extensive inflammation in premature infants. TGF-β is a strong immune suppressor and a factor in breast milk, which has been shown to be protective against NEC. In an NEC animal model, oral administration of the isoform TGF-β1 activated the downstream effector Smad2 in intestine and significantly reduced NEC incidence. In addition, TGF-β1 suppressed NF-κB activation, maintained levels of the NF-κB inhibitor IκBα in the intestinal epithelium, and systemically decreased serum levels of IL-6 and IFN-γ. The immature human fetal intestinal epithelial cell line H4 was used as a reductionistic model of the immature enterocyte to investigate mechanism. TGF-β1 pretreatment inhibited the TNF-α-induced IκBα phosphorylation that targets the IκBα protein for degradation and inhibited NF-κB activation. Chromatin immunoprecipitation (ChIP) assays demonstrated decreased NF-κB binding to the promoters of IL-6, IL-8, and IκBα in response to TNF-α with TGF-β1 pretreatment. These TGF-β1 effects appear to be mediated through the canonical Smad pathway as silencing of the TGF-β central mediator Smad4 resulted in loss of the TGF-β1 effects. Thus, TGF-β1 is capable of eliciting anti-inflammatory effects by inhibiting NF-κB specifically in the intestinal epithelium as well as by decreasing systemic IL-6 and IFN-γ levels. Oral administration of TGF-β1 therefore can potentially be used to protect against gastrointestinal diseases.
In vivo applications of magnetic nanoparticle hyperthermia

Abstract Hyperthermia is considered to be a promising tool for the treatment of tumours. Intensive research activities reveal a distinct impact not only on the cellular level but also on tumour physiology which favours the combination with the classical oncologic modalities radio- and chemotherapy. Different techniques have been established so far. Among them, magnetic hyperthermia exploits the intrinsic magnetic properties of iron oxide nanoparticles (magnetite and maghemite) which induce heating during the exposure to an alternating magnetic field. Beyond the advantage that heating is generated within the tumour and not from outside the body, the amounts of magnetic material and their intratumoral distribution patterns are key factors determining the therapeutic outcome. They can be influenced by the use of different application routes, which will be discussed in this paper.
The mammalian Cut homeodomain protein functions as a cell‐cycle‐dependent transcriptional repressor which downmodulates p21WAF1/CIP1/SDI1 in S phase

Cut is a homeodomain transcription factor which has the unusual property of containing several DNA‐binding domains: three regions called Cut repeats and the Cut homeodomain. Genetic studies in Drosophila melanogaster indicate that cut plays important roles in the determination and maintenance of cell‐type specificity. In the present study, we show that mammalian Cut proteins may yet play another biological role, specifically in proliferating cells. We found that the binding of Cut to a consensus binding site varies during the cell cycle. Binding was virtually undetectable in G0 and early G1, but became very strong as cells reached S phase. This was shown to result both from an increase in Cut expression and dephosphorylation of the Cut homeodomain by the Cdc25A phosphatase. We also show that the increase in Cut activity coincides with a decrease in p21WAF1/CIP1/SDI1 mRNAs. In co‐transfection experiments, Cut proteins repressed p21WAF1/CIP1/SDI1 gene expression through binding to a sequence that overlaps the TATA box. Moreover, p21WAF1/CIP1/SDI1 expression was repressed equally well by either Cdc25A or Cut. Altogether, these results suggest a model by which Cdc25A activates the Cut repressor which then downregulates transcription of p21WAF1/CIP1/SDI1 in S phase. Thus, in addition to their role during cellular differentiation, Cut proteins also serve as cell‐cycle‐dependent transcriptional factors in proliferating cells.
Relative Replicative Fitness of Human Immunodeficiency Virus Type 1 Mutants Resistant to Enfuvirtide (T-20)

ABSTRACT Resistance to enfuvirtide (ENF; T-20), a fusion inhibitor of human immunodeficiency virus type 1 (HIV-1), is conferred by mutations in the first heptad repeat of the gp41 ectodomain. The replicative fitness of recombinant viruses carrying ENF resistance mutations was studied in growth competition assays. ENF resistance mutations, selected in vitro or in vivo, were introduced into the env gene of HIV-1NL4-3 by site-directed mutagenesis and expressed in HIV-1 recombinants carrying sequence tags in nef. The doubling time of ENF-resistant viruses was highly correlated with decreasing ENF susceptibility (R2 = 0.859; P < 0.001). Initial fitness experiments focused on mutants identified by in vitro selection in the presence of ENF (L. T. Rimsky, D. C. Shugars, and T. J. Matthews, J. Virol. 72:986-993, 1998). In the absence of drug, these mutants displayed reduced fitness compared to wild-type virus with a relative order of fitness of wild type > I37T > V38 M > D36S/V38 M; this order was reversed in the presence of ENF. Likewise, recombinant viruses carrying ENF resistance mutations selected in vivo displayed reduced fitness in the absence of ENF with a relative order of wild type > N42T > V38A > N42T/N43K ≈ N42T/N43S > V38A/N42D ≈ V38A/N42T. Fitness and ENF susceptibility were inversely correlated (r = −0.988; P < 0.001). Similar results were obtained with recombinants expressing molecularly cloned full-length env genes obtained from patient-derived HIV-1 isolates before and after ENF treatment. Further studies are needed to determine whether the reduced fitness of ENF-resistant viruses alters their pathogenicity in vivo.
Aquifer Reclamation Design: Combined Simulation-Optimization Approach

A simulation-management methodology is demonstrated for the rehabilitation of aquifers that have been subjected to seawater intrusion. Finite difference groundwater flow and solute transport simulation are combined with nonlinear optimization. The model is capable of determining well locations plus pumping and injection rates of groundwater quality control. Restrictions was placed on hydraulic heads and concentrations. These restrictions was distributed over space and time. Two design strategies such as optimal pumping and recharge rates are demonstrated for a polluted aquifer. The method is not limited to these cases. It is generally applicable to the optimization of many types of distributed parameter systems.
Trust Your Instincts: The Relationship Between Intuitive Decision Making And Happiness

Epstein (1994; 2003) proposed that there are two cognitive information processing systems that operate in parallel: the intuitive thinking style and the rational thinking style. Decisional fit occurs when the preferred thinking style is applied to making a decision and research has shown that this fit increases the value of the outcome of a decision. Additionally, decisional fit leads to less regret, even when post hoc evaluations show the decision to be incorrect. It has not yet been determined whether decisional fit correlates with greater happiness and hence, the purpose of the current study was to investigate the difference between styles of thinking, styles of decision making and the impact of decisional fit on happiness scores. Individual differences in thinking and decision style were measured using an online interactive questionnaire (N = 100), and an ANOVA, hierarchical multiple regression, and a series of t-tests, were used to investigate the relationship between thinking style, decision style, decisional fit, and happiness, thereby addressing a gap in the existing literature. The major findings from the current study show that intuitive thinking has a strong positive correlation with happiness; that intuitive thinkers are more likely to utilize intuitive decisional style, than rational thinkers; and that when both rational and intuitive thinkers experienced decisional fit, higher ratings of happiness were reported. Explanations and recommendations for future studies are outlined in the discussion.
Protein kinase networks regulating glucocorticoid-induced apoptosis of hematopoietic cancer cells: fundamental aspects and practical considerations

Glucocorticoids (GCs) are integral components in the treatment protocols of acute lymphoblastic leukemia, multiple myeloma, and non-Hodgkin lymphoma owing to their ability to induce apoptosis of these malignant cells. Resistance to GC therapy is associated with poor prognosis. Although they have been used in clinics for decades, the signal transduction pathways involved in GC-induced apoptosis have only partly been resolved. Accumulating evidence shows that this cell death process is mediated by a communication between nuclear GR affecting gene transcription of pro-apoptotic genes such as Bim, mitochondrial GR affecting the physiology of the mitochondria, and the protein kinase glycogen synthase kinase-3 (GSK3), which interacts with Bim following exposure to GCs. Prevention of Bim up-regulation, mitochondrial GR translocation, and/or GSK3 activation are common causes leading to GC therapy failure. Various protein kinases positively regulating the pro-survival Src–PI3K–Akt–mTOR and Raf–Ras–MEK–ERK signal cascades have been shown to be activated in malignant leukemic cells and antagonize GC-induced apoptosis by inhibiting GSK3 activation and Bim expression. Targeting these protein kinases has proven effective in sensitizing GR-positive malignant lymphoid cells to GC-induced apoptosis. Thus, intervening with the pro-survival kinase network in GC-resistant cells should be a good means of improving GC therapy of hematopoietic malignancies.
Saccadic Reaction Times of Dyslexic and Age-Matched Normal Subjects

Saccadic reaction times (SRT) were measured in a simple task: subjects had to make saccades from a central fixation point to peripheral targets, which appeared randomly 4 deg to the left or to the right. In the first test the fixation point went off before the target appeared (gap trials); in the second test it remained on the screen (overlap trials). The distribution of SRTs for trained normal adults (N = 4), untrained normal adults (N = 11), untrained normal children (aged 9–11 years, N = 9), untrained normal teenagers (aged 15–17 years, N = 8), dyslexic children (aged 9–11 years, N = 15), and dyslexic teenagers (aged 15–17 years, N = 5) were compared, with special emphasis on the number of express saccades, ie saccades with extremely short reaction times (100–120 ms, under the present conditions). In normal adults with the gap paradigm, the distribution of reaction times typically exhibits two or three modes (express saccades, fast regular saccades, and very few slow regular saccades), whereas in the overlap paradigm only one or two modes (few fast regular saccades and many slow regular saccades) are obtained. On average, normal children produce more express saccades than naive normal adults. Dyslexic children produce more express saccades than the normal age-matched controls. Among the dyslexic children, four different types of abnormalities in their reaction times were encountered. The group of dyslexic teenagers was characterized by a larger number of express saccades at the expense of fast regular saccades in gap trials and by fewer express saccades and fewer fast regular saccades in overlap trials when compared to the age-matched control group. It is concluded that the abnormal patterns of saccadic reaction times reflect defects in the system of visual attention and/or in its control over the oculomotor system, rather than indicating a defect in the oculomotor system itself. In this context, symptoms of dyslexia appear as a combination of attentional deficits and irregular timing of saccadic eye movements.
Reliability of Freeway Traffic Flow: A Stochastic Concept of Capacity

This paper describes how conventional measures of effectiveness for freeway facilities usually reflect travel time in the form of e.g. travel velocity or delay. The paper describes how, it has recently been becoming more and more obvious that these parameters are not sufficient for freeway traffic performance assessments because they place great emphasis on smaller differences in travel time, whereas the more significant difference between flowing traffic and congestion is not adequately represented in the paper. It addition, traditional quality assessment fails whenever demand exceeds capacity because it will simply attest a failure in this case. However, temporary freeway overloads are quite common. This is why quality assessments for different degrees of freeway congestion are required as well. The capacity of a freeway is traditionally treated as a constant value in traffic engineering guidelines around the world, such as the HCM (2000). Doubts about this nature of capacities as constant values were raised by Ponzlet (1996) who demonstrated that capacities vary according to external conditions like dry or wet road surfaces, daylight or darkness, and prevailing purpose of the freeway (long distance or metropolitan commuter traffic).
Aflatoxins and Their Impact on Human and Animal Health: An Emerging Problem

Aspergillus is a fungus that essentially belongs to grains storage flora. It grows optimally at 25 °C with a minimum necessary water activity of 0.75. It starts to produce secondary metabolites at 10-12 oC, but the most toxic ones are produced at 25°C with a water activity of 0.95 (Hesseltine 1976). Those toxic secondary metabolites named aflatoxins (AF) is a group of mycotoxins produced by a large number of Aspergillus species, basically by three phylogenetically distinct sections. The main producers are A. flavus, and A. parasiticus, but it has been demonstrated that A. nomius, A. pseudotamarii, A. parvisclerotigenus, and A.bombycis of section Flavi, A. ochraceoroseus and A. rambellii from section Ochraceorosei and Emericella astellata and E. venezuelensis from Nidulatans section also generate aflatoxins (IARC 2002; Frisvad et. al., 2005). All of them contaminate a large fraction of the world’s food, including maize, rice, sorghum, barley, rye, wheat, peanut, groundnut, soya, cottonseed, and other derivative products made from these primary feedstuffs in low-income countries (Rizzi et al., 2003; Saleemullah et al., 2006; Strosnider et. al., 2006; Masoero et. al., 2007; Caloni, 2010). Although aflatoxins have been a problem throughout history, until 1960 they have been recognized as significant contaminants within agriculture, because in this year they were initially isolated and identified as the causative toxins in “Turkey-X-disease” after 100,000 turkeys died in England from an acute necrosis of the liver and hyperplasia of the bile duct after consuming groundnuts infected with Aspergillus flavus (Asao et. al., 1965; D’Mello, 1997; Strosnider et. al., 2006). Williams et al. estimated in 2004 that 4.5 billion of the world’s population is exposed to aflatoxins because they are also everywhere. Some essential factors that affect aflatoxin contamination include the climate of the region, the genotype of the crop planted, the soil type, the minimum and maximum daily temperatures, and the daily net evaporation (Strosnider et. al., 2006). Moreover, aflatoxin contamination is also promoted by stress or damage to the crop due to drought before harvest, the insect activity, a poor timing of harvest, the heavy rains during and after harvest, and an inadequate drying of the crop before storage. Levels of humidity, temperature, and aeration during storage are also important factors that are
A qualitative study of patients' views on anxiety and depression.

BACKGROUND In the management of patients with anxiety and depression in general practice, the emphasis has been on improving detection and appropriate use of drug therapies by health professionals. Patients' own perceptions of their problems and what services they would prefer have not often been sought. AIM To explore patient perspectives in relation to their healthcare needs in anxiety and depression. DESIGN OF STUDY Semi-structured individual and focus group interviews. SETTING A total of 27 patients from an urban four-partner group general practice who were identified as having anxiety and depression by a practice population questionnaire survey. METHOD All interviews were transcribed and the major themes were summarised using grounded theory analysis. RESULTS Patients seek many different ways of coping with their problems but view their general practice as a focal point for help. Their experiences are dominated by the struggle to control unwelcome and intrusive thoughts and to live in a hostile and threatening world. They also have distinct preferences regarding their health needs and there is universal scepticism about drug therapies. CONCLUSION Patients describe personal and professional barriers to seeking help and have particular views on the treatment options. This perspective contrasts with the current professional emphasis on detection and drug use. This view is therefore central to informing the debate on management of neurotic disorders in primary care and on improving the care of these patients.
Search Policies in Multi-Player Games

In this article we investigate how three multi-player search policies, namely maxn, paranoid, and Best-Reply Search, can be embedded in the MCTS framework. The performance of these search policies is tested in four different deterministic multi-player games with perfect information by running self-play experiments. We show that MCTS with the maxn search policy overall performs best. Furthermore, we introduce a multi-player variant of the MCTS-Solver. We propose three update rules for solving nodes in a multi-player MCTS tree. The experimental results show that the multi-player variant of the MCTS-Solver is a genuine improvement for MCTS in multi-player games.
Functional and molecular characterization of metabotropic glutamate receptors expressed in rat striatal cholinergic interneurones

In the present study we have used single‐cell RT‐PCR in conjunction with electrophysiology to examine the expression and functional properties of metabotropic glutamate receptors (mGluRs) expressed within biochemically identified cholinergic interneurones in the rat striatum. Using single‐cell RT‐PCR, it was possible to demonstrate the presence of mGluR1, mGluR2, mGluR3, mGluR5 and mGluR7 mRNAs within single cholinergic interneurones. Bath application of the non‐selective mGluR agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD) or the group‐I mGluR agonist 3,5‐dihydroxyphenylglycine (DHPG) depolarized all cholinergic neurones tested by activation of an inward current at − 60 mV. The effects of DHPG were partially inhibited by the mGluR5 selective antagonist 6‐methyl‐2‐(pherazo)‐3‐pyridinol and by the non‐selective group‐I antagonist α‐methyl‐4‐carboxyphenylglycine but were not mimicked by the group‐II and group‐III selective mGluR agonists 2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV) and l‐2‐amino‐4‐phosphonobutanoate (l‐AP4), respectively. Intrastriatal stimulation evoked an excitatory postsynaptic current within cholinergic neurones that was reversibly inhibited by bath application of the group‐II and group‐III selective mGluR agonists DCG‐IV and l‐AP4, respectively, via presynaptic actions.