Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Specific Glucose-Control Strategies on Microvascular and Macrovascular Outcomes in 58,000 Adults With Type 2 Diabetes

OBJECTIVE Comparative effectiveness research methods are used to compare the effect of four distinct glucose-control strategies on subsequent myocardial infarction and nephropathy in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 58,000 adults with type 2 diabetes and A1C <7% (53 mmol/mol) while taking two or more oral agents or basal insulin had subsequent A1C ≥7% (53 mmol/mol) to 8.5% (69 mmol/mol). Follow-up started on date of first A1C ≥7% and ended on date of a specific clinical event, death, disenrollment, or study end. Glucose-control strategies were defined as first intensification of glucose-lowering therapy at A1C ≥7, ≥7.5, ≥8, or ≥8.5% with subsequent control for treatment adherence. Logistic marginal structural models were fitted to assess the discrete-time hazards for each dynamic glucose-control strategy, adjusting for baseline and time-dependent confounding and selection bias through inverse probability weighting. RESULTS After adjustment for age, sex, race/ethnicity, comorbidities, blood pressure, lipids, BMI, and other covariates, progressively more aggressive glucose-control strategies were associated with reduced onset or progression of albuminuria but not associated with significant reduction in occurrence of myocardial infarction or preserved renal function based on estimated glomerular filtration rate over 4 years of follow-up. CONCLUSIONS In a large representative cohort of adults with type 2 diabetes, more aggressive glucose-control strategies have mixed short-term effects on microvascular complications and do not reduce the myocardial infarction rate over 4 years of follow-up. These findings are consistent with the results of recent clinical trials, but confirmation over longer periods of observation is needed.
Discovery of Massive Evolved Galaxies at z > 3 in the Hubble Ultra Deep Field

We have identified six early-type galaxies at z > 2.8 in the central 5.76 arcmin2 Hubble Ultra Deep Field NICMOS region based on a pronounced broadband discontinuity between the NICMOS F110W and F160W bandpasses. These galaxies have red observed optical and near-infrared colors (ABF775W - ABF160W ≥ 2) that cannot be explained entirely by dust reddening (indicating advanced age), and their luminosities at rest-frame optical wavelengths suggest a substantial stellar mass. One of the galaxies is detected in the X-ray and is likely to have an active nuclear region, while the rest are estimated to be at least 1 Gyr old at z ≈ 3 and contain a total stellar mass of (0.4-9.1) × 1010 h-2 M☉. We calculate a cumulative comoving stellar mass density of ρstar = (0.7-1.2) × 107 h M☉ Mpc-3 for massive evolved galaxies of M > 109 h-2 M☉ at z > 2.5. Comparison of the stellar mass density confined in galaxies of different types shows that massive evolved galaxies contribute ≈16%-28% of total stellar mass density even at these early epochs. Finally, an analysis of their morphology observed in the ACS and NICMOS images shows that the active galaxy has compact structure, while the rest are less concentrated. The presence of massive evolved galaxies at z ~ 3, when the universe was only 2 Gyr old, suggests that early star formation may have been particularly efficient in massive halos.
A Linearly Convergent Conditional Gradient Algorithm with Applications to Online and Stochastic Optimization

Linear optimization is many times algorithmically simpler than non-linear convex optimization. Linear optimization over matroid polytopes, matching polytopes and path polytopes are example of problems for which we have simple and efficient combinatorial algorithms, but whose non-linear convex counterpart is harder and admits significantly less efficient algorithms. This motivates the computational model of convex optimization, including the offline, online and stochastic settings, using a linear optimization oracle. In this computational model we give several new results that improve over the previous state-of-the-art. Our main result is a novel conditional gradient algorithm for smooth and strongly convex optimization over polyhedral sets that performs only a single linear optimization step over the domain on each iteration and enjoys a linear convergence rate. This gives an exponential improvement in convergence rate over previous results. Based on this new conditional gradient algorithm we give the first algorithms for online convex optimization over polyhedral sets that perform only a single linear optimization step over the domain while having optimal regret guarantees, answering an open question of Kalai and Vempala, and Hazan and Kale. Our online algorithms also imply conditional gradient algorithms for non-smooth and stochastic convex optimization with the same convergence rates as projected (sub)gradient methods.
Mucin1 shifts Smad3 signaling from the tumor-suppressive pSmad3C/p21WAF1 pathway to the oncogenic pSmad3L/c-Myc pathway by activating JNK in human hepatocellular carcinoma cells

Mucin1 (MUC1) is a transmembrane glycoprotein that acts as an oncogene in human hepatic tumorigenesis. Hepatocellular carcinoma (HCC) cells often gain advantage by reducing the tumor-suppressive activity of transforming growth factor beta (TGF-β) together with stimulation of its oncogenic activity as in MUC1 expressing HCC cells; however, molecular mechanisms remain largely unknown. Type I TGF-β receptor (TβRI) and c-Jun NH2-terminal kinase (JNK) differentially phosphorylate Smad3 mediator to create 2 phosphorylated forms: COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Here, we report that MUC1 overexpression in HCC cell lines suppresses TβRI-mediated pSmad3C signaling which involves growth inhibition by up-regulating p21WAF1. Instead, MUC1 directly activates JNK to stimulate oncogenic pSmad3L signaling, which fosters cell proliferation by up-regulating c-Myc. Conversely, MUC1 gene silencing in MUC1 expressing HCC cells results in preserved tumor-suppressive function via pSmad3C, while eliminating pSmad3L-mediated oncogenic activity both in vitro and in vivo. In addition, high correlation between MUC1 and pSmad3L/c-Myc but not pSmad3C/p21WAF1 expression was observed in HCC tissues from patients. Collectively, these results indicate that MUC1 shifts Smad3 signaling from a tumor-suppressive pSmad3C/p21WAF1 to an oncogenic pSmad3L/c-Myc pathway by directly activating JNK in HCC cells, suggesting that MUC1 is an important target for HCC therapy.
Cost-benefit analysis of a strategy to vaccinate healthy working adults against influenza.

BACKGROUND Influenza is a major cause of illness, disruption to daily life, and work absenteeism among healthy working adults aged between 18 and 64 years. This group is not included among the traditional priority groups for annual vaccination. Immunization rates remain low. OBJECTIVE To assess the economic implications of a strategy for annual vaccination of this group. METHODS Using the societal perspective, this cost-benefit analysis included the direct and indirect costs associated with vaccination as well as the direct and indirect costs prevented by vaccination. Clinical and economic variable estimates were derived primarily from the published literature. For this model, it was assumed that vaccination occurred in efficient, low-cost settings such as at the work site. Monte Carlo simulation was used to calculate the mean net costs or savings along with the 95% probability interval, and sensitivity analyses explored the sensitivity of the cost model to different values of the input variables. RESULTS Vaccinating healthy working adults was on average cost saving, with mean savings of $13.66 per person vaccinated (95% probability interval: net savings of $32.97 to net costs of $2.18), with vaccination generating net savings 95% of the time. The model was most sensitive to the influenza illness rate, the work absenteeism rate due to influenza, and hourly wages. In the worst-case scenario vaccination was not cost saving. Vaccination also generated net costs to society during years with a poor vaccine-circulating virus strain match. In all of the other sensitivity analysis scenarios, vaccination was cost saving. CONCLUSION Influenza vaccination of healthy working adults on average is cost saving. These findings support a strategy of routine, annual vaccination for this group, especially when vaccination occurs in efficient and low-cost sites.
Stress-Strain Behavior of Mortar Mixtures Containing Construction and Demolition Waste as Fine Aggregate

In this paper it was investigated how the use of recycled fine aggregate influences the stress-strain behavior of mortar mixtures with different strengths. The mix design composition of the studied mortars, expressed by mass, were 1:2:0.45, 1:4:0.68 and 1:6:1.05 (cement: sand: water/cement ratio). The substitution percentages by mass of the natural aggregate by recycled aggregate were 15, 25 and 50%. The recycled aggregate had a grain size distribution comparable to that of natural sand and was obtained by grinding the waste produced by the partial demolition of UFRJ’s University Hospital. The mortars were evaluated under uniaxial compressive strength test after 28 days of curing. The results indicated that for the two higher strength classes the substitution rates affects its mechanical response by decreasing the strength. Besides, for the lower strength class the recycled aggregate could promote an increase of strength in the case of 25% of replacement.
Clinical Validation of Point-Source Corneal Topography in Keratoplasty

Purpose. To validate the clinical performance of point-source corneal topography (PCT) in postpenetrating keratoplasty (PKP) eyes and to compare it with conventional Placido-based topography. Methods. Corneal elevation maps of the anterior corneal surface were obtained from 20 post-PKP corneas using PCT (VU topographer, prototype; VU University Medical Center, Amsterdam, The Netherlands) and Placido-based topography (Keratron, Optikon 2000, Rome, Italy). Corneal surface parameters are calculated in terms of radius and asphericity. Corneal aberrations were characterized using standard Zernike convention. An artificial surface with quadrafoil feature (SUMIPRO, Almelo, The Netherlands) was measured and used as a reference to assess instrument performance compared with the gold standard. Results. The differences (mean ± std of PCT − Placido) found between the two types of topographers in measurements of post-PKP eyes are 0.02 ± 0.21 mm (p = 0.64) for radius of curvature, 0.14 ± 0.49 (p = 0.23) for asphericity, −0.19 ± 1.67 &mgr;m (p = 0.61) for corneal astigmatism, −0.25 ± 1.34 &mgr;m (p = 0.41) for corneal coma, 0.23 ± 0.82 &mgr;m (p = 0.23) for corneal trefoil, and 0.15 ± 0.28 &mgr;m (p = 0.02) for corneal quadrafoil. The PCT measured the artificial surface more accurate (rms error 0.16 &mgr;m; 0.12 eq. Dpt.) than the Placido-based topographer (rms error 1.50 &mgr;m; 1.15 eq. Dpt.). Conclusions. PCT is more accurate than Placido-based topography in measuring quadrafoil aberration.
Clinical and neuropsychological correlates of impaired awareness of deficits in Alzheimer disease and Parkinson disease: a comparative study.

OBJECTIVE To compare patients with Alzheimer disease (AD) and Parkinson disease (PD) with regard to their awareness of cognitive, emotional/social interaction, self-care, and motor-related neurologic deficits. BACKGROUND Unawareness of deficits, a clinically important symptom, is found in AD. It has been hypothesized to be associated with disruption of frontal-subcortical circuits but has been little studied in other neurodegenerative disorders. Because PD has a different anatomic-pathologic substrate, a comparison of impairment of awareness in AD and PD may shed light on the neural basis of this phenomenon. METHOD Impairment of awareness was measured as the difference between patient self-report and caregiver ratings of patient abilities on questionnaires tapping cognitive, emotional/social interaction, self-care, and motor function. These "discrepancy scores" were then compared between the two diagnostic groups and examined in relation to selected neuropsychological test data. RESULTS In general, both AD and PD patients rate themselves as being less impaired than do their caregivers. The two diagnostic groups, AD and PD, differ significantly, however, on awareness discrepancy measures in the cognitive domain. In their ratings of patient cognitive skills, AD caregivers rate patients as significantly more impaired than patients rate themselves, whereas PD caregivers and patients do not differ significantly on these ratings. Impaired awareness in PD but not in AD is associated with poorer overall cognitive function and performance on tests measuring memory, attention, and constructional ability. CONCLUSIONS Both AD and PD patients display impaired awareness of deficits in multiple domains, including motor-related neurologic function. Parkinson disease patients with comparatively intact cognitive function display relatively preserved awareness of motor and other deficits.
Disambiguation Protocols Based on Risk Simulation

Suppose there is a need to swiftly navigate through a spatial arrangement of possibly forbidden regions, with each region marked with the probability that it is, indeed, forbidden. In close proximity to any of these regions, you have the dynamic capability of disambiguating the region and learning for certain whether or not the region is forbidden - only in the latter case may you proceed through that region. The central issue is how to most effectively exploit this disambiguation capability to minimize the expected length of the traversal. Regions are never entered while they are possibly forbidden, and thus, no risk is ever actually incurred. Nonetheless, for the sole purpose of deciding where to disambiguate, it may be advantageous to simulate risk, temporarily pretending that possibly forbidden regions are riskily traversable, and each potential traversal is weighted with its level of undesirability, which is a function of its traversal length and traversal risk. In this paper, the simulated risk disambiguation protocol is introduced, which has you follow along a shortest traversal - in this undesirability sense - until an ambiguous region is about to be entered; at that location, a disambiguation is performed on this ambiguous region. (The process is then repeated from the current location, until the destination is reached.) We introduce the tangent arc graph as a means of simplifying the implementation of simulated risk disambiguation protocols, and we show how to efficiently implement the simulated risk disambiguation protocols that are based on linear undesirability functions. The effectiveness of these disambiguation protocols is illustrated with examples, including an example that involves mine countermeasures path planning.
Coxsackievirus B3 Infects the Bone Marrow and Diminishes the Restorative Capacity of Erythroid and Lymphoid Progenitors

ABSTRACT Coxsackievirus B3 (CVB3) is known to infect stem cells in the neonatal central nervous system. Here, we evaluated the effects of CVB3 infection on the major source and repository of stem cells, the bone marrow (BM). Viral genome was detectable in BM within 24 h of infection, and productive infection of BM cells was evident, peaking at 48 h postinfection (p.i.), when ∼1 to 2% of BM cells produced infectious virus particles. Beginning at 2 to 3 days p.i. , a dramatic and persistent loss of immature erythroid cells, B and T lymphocytes, and neutrophils was observed in BM and, by day 3 to 4 p.i. , the femoral BM stroma was largely destroyed. Analysis of peripheral blood revealed a modest neutrophilia, a loss of reticulocytes, and a massive lymphopenia. The abundance of multipotent progenitor cells (Lin−/c-kit+/Flt3+) in BM declined ∼10-fold during CVB3 infection and, consistent with a deficiency of primitive hematopoietic progenitors, serum levels of the hematopoietic growth factor Flt3 ligand were dramatically elevated. Therefore, we analyzed the regenerative capacity of BM from CVB3-infected mice. Granulocyte/macrophage progenitors displayed a relatively normal proliferative ability, consistent with the fact that the peripheral blood level of neutrophils—which are very short-lived cells—remained high throughout infection. However, erythroid and lymphoid hematopoietic progenitors in BM from CVB3-infected mice showed a markedly reduced colony-forming capacity, consonant with the observed loss of both lymphocytes and immature erythroid cells/reticulocytes from the BM and peripheral blood. In summary, CVB3 infects the BM and exerts differential effects on the various hematopoietic progenitor populations.
The Effective Action of N=8 Supergravity

We present a simple form of the on-shell gauge-invariant 1-loop effective action of N=8 supergravity which is manifestly N=8 supersymmetric at the linear level. By generalizing the dimensional arguments in superspace to non-local invariants, we show that the 1-loop effective action does not contain any contributions from bubble and triangle diagrams. The absence of bubbles implies the absence of conformal and axial anomalies. We also show that the 1-loop effective action of N=8 supergravity features a "dual" conformal symmetry in the momentum space.
Design Principles for Flexible Systems

A fundamental aspect of designing systems with dedicated servers is identifying and improving the system bottlenecks. We extend the concept of a bottleneck to networks with heterogeneous, flexible servers. In contrast with a network with dedicated servers, the bottlenecks are not a priori obvious, but can be determined by solving a number of linear programming problems. Unlike the dedicated server case, we find that a bottleneck may span several nodes in the network. We then identify some characteristics of desirable flexibility structures. In particular, the chosen flexibility structure should not only achieve the maximal possible capacity (corresponding to full server flexibility), but should also have the feature that the entire network is the (unique) system bottleneck. The reason is that it is then possible to shift capacity between arbitrary nodes in the network, allowing the network to cope with demand fluctuations. Finally, we specify when certain flexibility structures (in particular chaining, targeted flexibility, and the �N� and �W� structures from the call center literature) possess these desirable characteristics.
The Biphasic Effects of Moderate Alcohol Consumption with a Meal on Ambiance-Induced Mood and Autonomic Nervous System Balance: A Randomized Crossover Trial

Background The pre-drinking mood state has been indicated to be an important factor in the mood effects of alcohol. However, for moderate alcohol consumption there are no controlled studies showing this association. Also, the mood effects of consuming alcohol combined with food are largely unknown. The aim of this study was to investigate the effects of moderate alcohol combined with a meal on ambiance-induced mood states. Furthermore effects on autonomic nervous system activity were measured to explore physiological mechanisms that may be involved in changes of mood state. Methods In a crossover design 28 women (age 18–45 y, BMI 18.5–27 kg/m2) were randomly allocated to 4 conditions in which they received 3 glasses of sparkling white wine (30 g alcohol) or alcohol-free sparkling white wine while having dinner in a room with either a pleasant or unpleasant created ambiance. Subjects filled out questionnaires (B-BAES, POMS and postprandial wellness questionnaire) at different times. Skin conductance and heart rate variability were measured continuously. Results Moderate alcohol consumption increased happiness scores in the unpleasant, but not in the pleasant ambiance. Alcohol consumption increased happiness and stimulation feelings within 1 hour and increased sedative feelings and sleepiness for 2.5 hour. Skin conductance was increased after alcohol within 1 hour and was related to happiness and stimulation scores. Heart rate variability was decreased after alcohol for 2 hours and was related to mental alertness. Conclusion Mood inductions and autonomic nervous system parameters may be useful to evaluate mood changes by nutritional interventions. Moderate alcohol consumption elevates happiness scores in an unpleasant ambiance. However, drinking alcohol during a pleasant mood results in an equally positive mood state. Trial Registration Clinicaltrials.gov NCT01426022.
HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells

Hypoxia-inducible factor 1α (HIF-1α) expression is a hallmark of intratumoral hypoxia that is associated with breast cancer metastasis and patient mortality. Previously, we demonstrated that HIF-1 stimulates the expression and activity of TAZ, which is a transcriptional effector of the Hippo signaling pathway, by increasing TAZ synthesis and nuclear localization. Here, we report that direct protein-protein interaction between HIF-1α and TAZ has reciprocal effects: HIF-1α stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1α. Inhibition of TAZ expression impairs the hypoxic induction of HIF-1 target genes, such as PDK1, LDHA, BNIP3 and P4HA2 in response to hypoxia, whereas inhibition of HIF-1α expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1α and TAZ that increases their transcriptional activities in hypoxic cells.
Quantitative Study of Synaptophysin Immunoreactivity of Cerebral Cortex and Spinal Cord in Motor Neuron Disease

Synaptophysin immunoreactivity can be quantified by image analysis to evaluate loss of presynaptic terminals in human neurodegenerative diseases. The extent and regional distribution of such loss is reported in motor neuron disease (MND). Autopsy samples of spinal cord and cerebral cortex were examined from 28 cases of MND and 28 age and sex matched controls. The MND group included individuals with amyotrophic lateral sclerosis (17[ALS]), and progressive muscular atrophy (11[PMA]). In the spinal cord, there was significant reduction of presynaptic terminals in the lateral ventral horn (15%) in both the ALS (p<0.01) and PMA (p<0.05) groups. Perisomatic synaptophysin profiles on lower motor neurons are preserved late in the disease and are not related to corticospinal innervation. Less marked presynaptic loss was demonstrable more widely in the medial ventral, intermediate and dorsal spinal grey matter (10%) in both ALS (p=0.03) and PMA (p=0.05). In the cerebral cortex no synaptic loss was demonstrated in motor or anterior cingulate regions in any of the MND cases. Spinal degeneration in MND is associated with loss of presynaptic terminals in all grey matter regions. It is most marked in the limb motor neuron area and is independent of corticospinal tract degeneration. The cerebral pathology of ALS is not associated with significant loss of presynaptic terminals in the cortical areas studied.