Miracle-dz/UniFAR-FTUs huggingface dataset:
Response to a comment on ‘the risk of coronary heart disease in type 2 diabetic patients exposed to thiazolidinediones compared to metformin and sulfonylurea therapy’

PURPOSE To evaluate whether the risk of coronary heart disease (CHD) differs among adult diabetic patients treated with thiazolidinediones (TZDs) and similar patients treated with combined oral metformin and sulfonylurea (M + S) therapy. METHODS We conducted a retrospective cohort study involving 25 140 diabetic patients aged 18 and older who had at least one pharmacy claim for a TZD or combined M + S therapy between 1 January 1999 and 30 June 2002. We used propensity score matching to adjust for observable differences between initiators of combined M + S therapy and TZD initiators. The data were analyzed in two ways: first based on the original matched groups, 'as balanced', without accounting for switching to another medication during follow-up, and second based on actual antidiabetic drug use during follow-up, 'as treated'. Cox proportional hazards regression and multivariable Poisson regression were performed to compare the risk of CHD events. RESULTS In the 'as balanced' analysis, the risk for CHD among TZD users relative to combination drug users was close to the null value (adjusted hazard ratio: 1.02, 95% confidence intervals (CI): 0.87-1.20). In the 'as treated' analysis, the risk of CHD was similar for periods of current use of TZDs compared to periods of non-use (incidence rate ratio: 1.10, 95%CI: 0.96-1.25). CONCLUSIONS These results do not suggest a cardioprotective or deleterious effects of TZDs compared with combined M + S oral therapy on the short-term CHD event risk in persons with type 2 diabetes after accounting for the greater baseline CHD risk in TZD initiators.
Modeling radiation belt electron dynamics during GEM challenge intervals with the DREAM3D diffusion model

As a response to the Geospace Environment Modeling (GEM) “Global Radiation Belt Modeling Challenge,” a 3D diffusion model is used to simulate the radiation belt electron dynamics during two intervals of the Combined Release and Radiation Effects Satellite (CRRES) mission, 15 August to 15 October 1990 and 1 February to 31 July 1991. The 3D diffusion model, developed as part of the Dynamic Radiation Environment Assimilation Model (DREAM) project, includes radial, pitch angle, and momentum diffusion and mixed pitch angle‐momentum diffusion, which are driven by dynamic wave databases from the statistical CRRES wave data, including plasmaspheric hiss, lower‐band, and upper‐band chorus. By comparing the DREAM3D model outputs to the CRRES electron phase space density (PSD) data, we find that, with a data‐driven boundary condition at Lmax = 5.5, the electron enhancements can generally be explained by radial diffusion, though additional local heating from chorus waves is required. Because the PSD reductions are included in the boundary condition at Lmax = 5.5, our model captures the fast electron dropouts over a large L range, producing better model performance compared to previous published results. Plasmaspheric hiss produces electron losses inside the plasmasphere, but the model still sometimes overestimates the PSD there. Test simulations using reduced radial diffusion coefficients or increased pitch angle diffusion coefficients inside the plasmasphere suggest that better wave models and more realistic radial diffusion coefficients, both inside and outside the plasmasphere, are needed to improve the model performance. Statistically, the results show that, with the data‐driven outer boundary condition, including radial diffusion and plasmaspheric hiss is sufficient to model the electrons during geomagnetically quiet times, but to best capture the radiation belt variations during active times, pitch angle and momentum diffusion from chorus waves are required.
Chemotherapy ordering in a computerized physician order entry (CPOE) environment: A longitudinal analysis of defects from oncologist to patient.

6040 Background: While published data suggest low chemotherapy error rates, the rate of chemotherapy ordering process defects and who detects them remains uncertain. METHODS Outpatient treatment plans/orders were prospectively evaluated by pharmacy prior to preparation, then by nursing prior to administration. Data collected included the nature of defects, how detected, utility of regimen-specific care sets (facilitating antineoplastic dose calculation and adjunct agent selection), and patient impact. RESULTS Pharmacy recognized problems with 36% of orders (comprising 1,082 cycles/4,600 drugs), with 34% incomplete (absent orders 17%; missing cycle number 12.5%; other items 4%). Pharmacy identified incorrect orders in 6% (dose calculation 2%; cycle number 1.5%; other items 2.5%). Incomplete orders were more likely to have incorrect items (11.6% v. 3.5% if complete, p < .001). Care set use (76% of cycles) was associated with fewer overall problems and incomplete orders (both p < .001), with reduced absent orders and missing antiemetics, but not antineoplastics. Care set orders exhibited a trend for fewer incorrect items (p=.06). Nursing recognized problems with 14.6% of orders, again most commonly incomplete orders (10%; absent orders 7%; missing antiemetic or antineoplastic drug 4.6%); fewer missing items resulted from care set use (p < .001). Nursing detected fewer orders with problems and missing items but more instances of missing antineoplastic and antiemetic agents (all p < .001) despite prior pharmacy review. Nursing identified incorrect orders in 5% (wrong dosage 3.4%; wrong drug 2.5%) and classified 4% of cycles as having an error ("near miss" 3.3%; more serious error reaching the patient 0.6%). CONCLUSIONS Defects in chemotherapy orders are common despite the relatively low error rate. The predominant defects-incomplete orders-are associated with incorrect items. Both care sets and pharmacy review reduce but do not eliminate incomplete orders; the effect on incorrect orders is smaller. Even with CPOE, sequential pharmacy and nursing review remain critical to reducing order defects; additional software enhancements are needed to further reduce defects. No significant financial relationships to disclose.
Identifying Sociodemographic Characteristics Associated With Burden Among Caregivers of the Urban Homebound

Limited research has explored whether the burden associated with caring for homebound patients varies across racial groups or by relationship status. We examined these variations for this vulnerable population. Patients self-identified informal caregivers and caregiver burden/depression were assessed using the Zarit Caregiver Burden Scale and the Center for Epidemiologic Studies–Depression scale (CES-D). Forty-nine informal caregivers completed the interview. Mean age was 58 (SD = 14), 78% were female, 37% Black, 35% Hispanic, and 46% had completed high school. Over 60% of caregivers had moderate or severe caregiver burden and 30% had significant depression. White caregivers had greater burden than Black and Hispanic caregivers (p = .02). Mean caregiver burden was higher among spouse/partner caregivers, versus those who identified as children or other family or friends (p = .004). Additional research is needed to better understand the experience of racial and ethnic minorities and spouses in providing informal care to homebound adults.
A novel CYBA variant, the –675A/T polymorphism, is associated with essential hypertension

Objective Oxidative stress is implicated in hypertension and the NADPH oxidase systems constitute the main source of superoxide in vascular wall. We searched for new polymorphisms within the CYBA promoter, the human gene that encodes the p22phox protein, and studied their potential association with essential hypertension. Design A case–control study in a random sample of the general population. Methods CYBA polymorphisms were determined by restriction fragment length polymorphism and allelic discrimination. NADPH oxidase activity was quantified in phagocytic cells by chemiluminescence. Results We identified three novel polymorphisms, at positions –852, –675 and –536 from the ATG codon. Only the –675A/T polymorphism associated with essential hypertension. The prevalence of the TT genotype and the T allele frequency were significantly higher (P < 0.05) in hypertensives than in normotensives. Furthermore, TT hypertensives exhibited higher (P < 0.05) systolic blood pressure values than TA/AA hypertensives. Increased phagocytic NADPH oxidase activity was observed in TT subjects compared to TA and AA individuals (P < 0.05). Enhanced carotid intima–media thickness, a surrogate marker of atherosclerosis, was found in TT subjects compared to TA and AA individuals (P < 0.05). Finally, mutagenesis experiments demonstrated a functional role of this polymorphism on the CYBA promoter activity. Conclusion The –675A/T CYBA polymorphism may be a novel genetic marker associated with essential hypertension. Furthermore, TT subjects exhibit features of NADPH oxidase-mediated oxidative stress and asymptomatic atherosclerosis.
Two classes of single-input X-cells in cat lateral geniculate nucleus. II. Retinal inputs and the generation of receptive-field properties.

The retinal inputs to cells in the cat's lateral geniculate nucleus (LGN) were directly recorded to study the basis for the properties of two classes of LGN X-cells: Xs (single) and XL (lagged). The presence of excitatory or inhibitory input to an LGN cell from a particular simultaneously recorded ganglion cell was assessed with cross-correlograms during unstimulated activity. Because neighboring ganglion cells do not fire independently, features in a retinogeniculate correlogram can arise in two ways that must be distinguished by a direct effect of the ganglion cell on the LGN cell, or by correlated firing between that ganglion cell and some other ganglion cell that is an excitatory or inhibitory input to the LGN cell. It was possible to determine the origin of correlogram features because features indicating a retinogeniculate effect were distinctly different in timing and strength from features arising solely from correlated firing in the retina. The characteristic feature in a correlogram between an LGN cell and an excitatory retinal input was a sharp peak in LGN cell firing rate at the appropriate latency after the firing of the ganglion cell. The characteristic feature for an inhibitory input was a dip in LGN cell firing rate after the firing of the ganglion cell. Typically, this dip lasted 10-40 ms and was followed by a prolonged enhancement in LGN cell firing rate, which may reflect a postinhibitory rebound. XS-cells had a single retinal X input whose excitatory effect caused most of the LGN cell's spikes during stimulated and unstimulated activity. There was no conclusive evidence that any XS-cell received excitatory retinal input from either Y-cells or other X-cells of the same center sign. There was usually evidence for inhibition of XS-cells by retinal X-cells of opposite center sign with receptive fields highly overlapping that of the XS-cell, but rarely evidence for inhibition by Y-cells. XL-cells also had only a single excitatory input, but this X input had a relatively weak effect that caused only a minority of the LGN cell's spikes, typically 17% during maintained activity and 29% during visual stimulation. The input's excitatory effect was immediately followed by strong inhibition of the XL-cell. XL-cells were also inhibited by retinal X-cells of the same center sign that were adjacent (nearest neighbors) to the excitatory input. The strength and latency of both of these inhibitory effects indicate that the inhibition was disynaptic. (ABSTRACT TRUNCATED AT 400 WORDS)
Therapeutic effect of umbilical cord serum eyedrops for persistent corneal epithelial defect.

PURPOSE To evaluate the therapeutic effect of umbilical cord serum in the treatment of persistent epithelial defect of the cornea. METHODS Fourteen eyes of 14 patients with persistent epithelial defect that had persisted for at least 2 weeks despite conventional treatment were treated with 20% umbilical cord serum eyedrops six times a day. The images of the epithelial defects were captured using a camera attached to a slit lamp biomicroscope and the areas of the epithelial defects were calculated. Treatment was considered effective for epithelial defect healing within 2 weeks, partially effective for healing within 2 to 4 weeks, and ineffective for healing requiring either more than 1 month or additional measures. RESULTS Mean duration of epithelial defect before treatment was 7.2 +/- 6.3 weeks, and mean area was 7.86 +/- 7.32 mm2. Umbilical cord serum therapy was effective in 6 eyes (42.9%), partially effective in 6 (42.9%), and ineffective in 2 (14.2%). Nevertheless, the epithelial defects in both the ineffective eyes were eventually healed within 8 weeks. Mean healing time in effective or partially effective cases was 2.75 +/- 1.06 weeks. CONCLUSIONS The use of umbilical cord serum eyedrops for the treatment of persistent epithelial defect is effective.
Educational psychologists and youth offending services: Working together to improve the educational outcomes of young offenders. An action research project.

The poor educational outcomes of young people in the youth justice (YJ) system are well documented. In England, Youth Offending Services (YOSs) work with young offenders, and part of their remit is to engage them in education. Educational psychologists (EPs) aim to improve the educational outcomes of young people, using a range of psychological frameworks and tools. However, multi-agency practice between YOSs and EPs is under-developed. This project aims to explore how EPs may support YOSs, by answering the following research questions: a) What are the challenges and opportunities to youth offender education, both identified by research and from the perspective of YOS staff? b) What YOS activities can help to build upon opportunities and overcome the challenges? c) Can these activities be compiled into an evidence-informed self-review framework which will be implemented to inform YOS practice? d) To what extent can an evidence-informed self-review influence practice development between EPs and YOSs? An Action Research approach is taken. Following a review of relevant literature, to explore the perceived challenges and opportunities to youth offender education from the perspective of YOS staff, semi-structured interviews were conducted with staff (n=9) from an Inner London YOS. A Thematic Analysis was conducted. YOS and EPS case records were also analysed, to explore the extent to which EPs are involved with young people known to the YOS, and how much their involvement appears to impact on YOS practice. The TA identified five superordinate themes, relating to descriptions of the ROLES they, or other professionals fulfil, the STRENGTHS they perceive in the work, descriptions of YOUNG PEOPLE FACTORS and SYSTEMIC FACTORS which impede or facilitate educational progress, and the perceived NEEDS of the service. The analysis of case records suggested that information-sharing between the YOS and the EPS was limited. These findings were combined with a review of research into best practice in the education of young offenders, and used to create an evidence-informed self-evaluation framework. The framework allows YOSs to identify strengths and needs with regards to educational practice, and develop an action plan for improvement, including abstracting aspects of EP practice which may be helpful. The self-review process was piloted with the participating YOS, and reflections as to this experience and its utility, as well as recommendations for future practice, are provided.
Immunobiological activities of chemically defined lipid A from lipopolysaccharides of Porphyromonas gingivalis.

Immunobiological activities of chemically defined lipid A from lipopolysaccharides (LPS) of Porphyromonas gingivalis strain 381, which possesses beta-(1-->6)-linked glucosamine disaccharide 1-monophosphate, with 3-hydroxy-15-methylhexadecanoyl and 3-hexadecanoyloxy-15-methylhexadecanoyl groups at the 2- and 2'-positions, respectively, were compared with those of synthetic Escherichia coli-type lipid A (compound 506) and Salmonella-type lipid A (compound 516). P. gingivalis lipid A and its LPS induced stronger or comparable production of the cytokines interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and interferon-gamma as compared with compounds 506 and 516 in the culture supernatants of human peripheral blood monocytes or mononuclear cells. However, the P. gingivalis preparations showed low activity in inducing the production of IL-1 beta and tumour necrosis factor-alpha. Clear antagonistic effects of P. gingivalis lipid A and its LPS against IL-1 beta production induced by E. coli LPS or compound 506 were seen. Furthermore, P. gingivalis lipid A and its LPS had marked immunopharmacological activities, i.e. antitumour, natural killer cell and antiviral activities. Its monophosphorylation pattern and the presence and position of fatty acids possessing acyl chains of considerable length are unique to P. gingivalis lipid A, differing from enterobacterial lipid As. Its good balance between agonistic and antagonistic effects, making it a possible candidate for use as an immunomodulatory drug, may be attributable to these unique features.
Molecular Pathways: Human Leukocyte Antigen G (HLA-G)

Human leukocyte antigen G (HLA-G) is a nonclassical MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal, and breast cancers) and hematologic malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer, suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. As HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer. Elimination of HLA-G–expressing cancer cells would be important in the efficacy of anticancer therapies. Clin Cancer Res; 19(20); 5564–71. ©2013 AACR.
CD4+ T Cells of Schistosomiasis Naturally Resistant Individuals Living in an Endemic Area Produce Interferon‐γ and Tumour Necrosis Factor‐α in Response to The Recombinant 14kdaSchistosoma mansoni Fatty Acid‐Binding Protein

Cellular immune responses to recombinant (r) Sm14 were examined in chronic, treated patients and uninfected individuals living in an endemic area for schistosomiasis. The lymphocyte proliferative responses and cytokine profile to this antigen were evaluated. Peripheral blood mononuclear cells (PBMC) of all groups studied proliferated to rSm14. However, the highest proliferation index to rSm14 was detected in uninfected endemic normal (EN) individuals who are naturally resistant to schistosomiasis. Regarding the cytokines produced, the levels of interleukin (IL)‐5 and IL‐10, known as Th2 cytokines, were not statistically different among all groups studied. In contrast, interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α were produced in significantly higher amounts by PBMC of EN individuals following rSm14 stimulation. Additionally, we have determined by flow cytometry that CD4+ T cells from these individuals are the main lymphocyte subpopulation producing IFN‐γ and TNF‐α. Moreover, we have used rIL‐10 or rIFN‐γ, or monoclonal antibodies (MoAb) against these two cytokines to determine their role on cellular reactivity to rSm14. Exogenous IL‐10 suppressed T‐cell proliferation and neutralization of endogenous IL‐10 restored lymphocyte activation and enhanced IFN‐γ and TNF‐α production in chronically infected patients. In contrast, the addition of anti‐IFN‐γ totally abrogated the PBMC proliferation within the EN group. This study demonstrated that IL‐10 is an important cytokine down‐regulating T‐cell responses in chronic schistosomiasis, whereas lymphocyte proliferation in the uninfected resistant group is dependent on IFN‐γ. Taken together these results suggest that Th1 type of immune response induced in EN individuals to a specific schistosome antigen might be associated with resistance to infection and also highlighted the importance of Sm14 as a potential vaccine candidate.
Exchange-Traded Funds as an Alternative Investment Option: A Case Study

We conduct an analysis of Exchange-traded Funds (ETFs), Index and Equity mutual funds and their respective benchmark during the 2010-2015 period for the Portuguese fund industry. For the period 2010-2017 we test ETFs for price inefficiency (existence of deviations between prices and the Net Asset Value) and persistence. We find that ETF do not always outperform index funds in replicating the variations of the PSI 20 index, despite exhibiting better tracking ability when facing downside deviations of the benchmark and a better capacity of smoothing tracking deviations. Regarding ETFs price efficiency and its persistence, the study reveals that the analyzed ETF is priced at a low average discount with evidence of deviations persistence of at least two days. The investment schemes with the highest ability to track the PSI 20 Index were PSI20 (ETF), BBVA PPA Indice PSI20, and the equity mutual fund BPI Portugal.
Anomalous nuclear magnetic relaxation of aqueous solutions of ferritin: An unprecedented first‐order mechanism

Ferritin, the iron‐storing protein, speeds up proton transverse magnetic relaxation in aqueous solutions. This T2 shortening is used in MRI to quantify iron in the brain and liver. Current theoretical models underestimate the relaxation enhancement by ferritin at imaging fields, and they do not predict the measured dependence of the rate enhancement on the magnetization of the particles. Here it is shown that a proton exchange dephasing model (PEDM) overcomes these limitations by allowing a first‐order relaxation mechanism. The PEDM considers proton exchange between bulk water and exchangeable protons located at the surface of the hydrated iron oxide nanometric core of the protein. Relaxation is shown to depend on the distribution of the frequency shifts of the adsorption sites; the observed properties agree with a Lorentzian distribution. Computer simulations utilizing recent Mössbauer spectroscopy data show that the distribution of these shifts is effectively Lorentzian. Magn Reson Med 48:959–964, 2002. © 2002 Wiley‐Liss, Inc.