Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Study of Amnesic Patients at High Risk for Alzheimer’s Disease: Clinical, Neuropsychological and Magnetic Resonance Spectroscopy Features

Background/Aims: To prospectively follow up a group of amnesic patients at risk for Alzheimer’s disease (AD), to characterize a group of patients whose features were intermediate between amnesic mild cognitive impairment (aMCI) and probable AD, prodromal AD (Prd-AD), and to investigate if these patients were at higher risk for AD conversion. Methods: A total of 109 subjects were assessed by neuropsychological evaluation and by 1H magnetic resonance spectroscopy (1H-MRS): 27 controls, and 16 aMCI, 34 probable AD and 32 Prd-AD patients. Results: Episodic memory and frontal test scores resulted lower in Prd-AD compared to aMCI patients. Prd-AD patients obtained significantly higher scores than AD ones in language, perception, praxis and frontal functions. Although Prd-AD and AD patients had distinct 1H-MRS features from aMCI ones, there were no 1H-MRS differences between Prd-AD and AD patients. The AD annual conversion rate after 1 year of follow-up for Prd-AD (57.1%) was higher than in aMCI patients (20%; p < 0.01). A logistic regression, in which all amnesic patients were treated as a single group, showed that the Visual Memory Test was a significant neuropsychological predictor for AD conversion. Conclusions: Prd-AD patients are a clinically distinguishable group, with distinct neuropsychological and 1H-MRS features and a higher conversion rate to probable AD than aMCI patients.
A comparison of morning and evening instillation of a combination travoprost 0.004%/timolol 0.5% ophthalmic solution.

PURPOSE To compare the intraocular pressure lowering efficacy and side effect profile of travoprost 0.004%/timolol 0.5% ophthalmic solution dosed in the morning and evening. METHODS This was a multicenter, prospective, randomized, double-masked, parallel group clinical study of 92 patients with open-angle glaucoma (with or without pseudoexfoliative or pigmentary glaucoma) or ocular hypertension. After a washout of existing glaucoma medications, patients were randomly assigned to receive one drop of travoprost 0.004%/timolol 0.5% in the morning or evening for 6 weeks. The main outcome measures were mean intraocular pressure (IOP) assessed at 9 am, 11 am, and 4 pm, and safety variables. RESULTS Travoprost 0.004%/timolol 0.5% ophthalmic solution, dosed in the morning or evening, controlled IOP consistently throughout the day. Mean IOP ranged from 16.5 to 16.7 mmHg in the morning treatment group and from 16.1 to 17.2 mmHg in the evening treatment group. Travoprost 0.004%/timolol 0.5% ophthalmic solution produced statistically significant and clinically relevant reductions in IOP from baseline; mean reductions ranged from approximately 8 to 10 mmHg (32% to 38%). Travoprost 0.004%/timolol 0.5% ophthalmic solution was safe and well tolerated with the most frequently reported adverse event being ocular hyperemia, which occurred in 12.5% of patients in the morning treatment group and 13.6% of patients in the evening treatment group. CONCLUSIONS Travoprost 0.004%/timolol 0.5% given once daily, either in the morning or evening, is a safe and effective treatment for open-angle glaucoma and ocular hypertension. It may be beneficial for patients judged to be inadequately controlled on a prostaglandin analogue or ophthalmic beta-blocker alone.
Wage Rigidity: A Quantitative Solution to Several Asset Pricing Puzzles

In standard production models, wage volatility is far too high, and equity volatility is far too low. A simple modification–sticky wages because of infrequent resetting together with a constant elasticity of substitution (CES) production function leads to both smoother wages and higher equity volatility. Further, the model produces several other hard-to-explain features of financial data: high Sharpe ratios, low and smooth interest rates, time-varying equity volatility and premium, a value premium, and a downward-sloping equity term structure. Procyclical, volatile wages are a hedge for firms in standard models; smoother wages act like operating leverage, making profits and dividends riskier. Received July 30, 2013; accepted July 6, 2015 by Editor Geert Bekaert.
Organ-Specific Gene Expression Changes in the Fetal Liver and Placenta in Response to Maternal Folate Depletion

Growing evidence supports the hypothesis that the in utero environment can have profound implications for fetal development and later life offspring health. Current theory suggests conditions experienced in utero prepare, or “programme”, the fetus for its anticipated post-natal environment. The mechanisms responsible for these programming events are poorly understood but are likely to involve gene expression changes. Folate is essential for normal fetal development and inadequate maternal folate supply during pregnancy has long term adverse effects for offspring. We tested the hypothesis that folate depletion during pregnancy alters offspring programming through altered gene expression. Female C57BL/6J mice were fed diets containing 2 mg or 0.4 mg folic acid/kg for 4 weeks before mating and throughout pregnancy. At 17.5 day gestation, genome-wide gene expression was measured in male fetal livers and placentas. In the fetal liver, 989 genes were expressed differentially (555 up-regulated, 434 down-regulated) in response to maternal folate depletion, with 460 genes expressed differentially (250 up-regulated, 255 down-regulated) in the placenta. Only 25 differentially expressed genes were common between organs. Maternal folate intake during pregnancy influences fetal gene expression in a highly organ specific manner which may reflect organ-specific functions.
Test–retest reliability of skeletal muscle oxygenation measurements during submaximal cycling exercise in patients with chronic heart failure

The potential purpose of near‐infrared spectroscopy (NIRS) as a clinical application in patients with chronic heart failure (CHF) is the identification of limitations in O2 delivery or utilization during exercise. The objective of this study was to evaluate absolute and relative test–retest reliability of skeletal muscle oxygenation measurements in patients with CHF. Thirty patients with systolic heart failure (left ventricular ejection fraction 31 ± 8%) performed 6‐min constant‐load cycling tests at 80% of the anaerobic threshold (AT) with tissue saturation index (TSI) measurement at the vastus lateralis. Tests were repeated after 10 ± 5 days to evaluate reliability. Absolute reliability was assessed with limits of agreement (LoA, expressed as bias ± random error) and coefficients of variation (CV) for absolute values (LoA range: 0·4 ± 6·2% to 0·6 ± 7·9%; CV range: 4·7–7·1%), amplitudes (LoA range −0·5 ± 5·8% to −0·7 ± 6·8%; CV range: 26·2–42·1%), onset and recovery kinetics (mean response times; LoA 0·4 ± 9·5 s, CV 23·5% and LoA −5·8 ± 50·8 s, CV 67·4% respectively) and overshoot characteristics (CV range 45·7–208·6%). Relative reliability was assessed with intraclass correlation coefficients for absolute values (range 0·74–0·90), amplitudes (range 0·85–0·92), onset and recovery kinetics (0·53 and 0·51, respectively) and overshoot characteristics (range 0·17–0·74). In conclusion, absolute reliability of absolute values and onset kinetics seems acceptable for serial within‐subject comparison, and as such, for evaluation of treatment effects. Absolute reliability of amplitudes and recovery kinetics is considered unsatisfactory. Relative reliability of absolute values and amplitudes is sufficient for purposes of physiological distinction between patients with CHF. Despite lower relative reliability, kinetics may still be useful for clinical application.
Reductions in sexually transmitted infections associated with popular opinion leaders in China in a randomised controlled trial

Objectives A community level randomised controlled trial of a Community Popular Opinion Leader (C-POL) intervention to reduce bacterial and viral sexually transmitted infections (STIs) and unprotected extramarital sex was carried out over 2 years in five countries. The main study results did not find significant intervention effects. This paper presents a sub-analysis examining the differential intervention impacts among high-risk and low-risk participants in the China site. Methods From 2002 –2006, 3912 migrant market vendors aged 18 and 49 years were recruited at an urban site in China. Markets were randomly assigned to the C-POL intervention (N=20 markets; n=1979) or standard-care control condition (N=20; n=1933). Both study condition venues received HIV/STI education, free condoms, STI testing and treatment, and training for pharmacists in antibiotic treatments. In intervention markets, C-POLs were identified and trained to diffuse messages regarding safer sex, STI treatment and partner discussions of sex. The primary biological outcome was incidence of new STIs (chlamydia, gonorrhoea, syphilis, trichomonas, herpes or HIV). The primary sexual behaviour risk outcome was any unprotected extramarital sex in the prior 3 months. Results In unadjusted analyses, women had significantly lower rates of STI infection at 24 months in the C-POL intervention (5.7%) compared to controls (8.3%; p=0.043). In mixed-effects regression models, intervention participants with STIs at previous assessments were about half as likely to have STIs at 24 months (OR 0.47, 95% CI 0.25 to 0.90) compared to controls. Conclusions The C-POL intervention lowers HIV risk among those at highest risk (ie, with a STI or engaging in high-risk sexual activities) rather than the general population. Trial registration http://Clinicaltrials.gov/ identifier NCT 00710060.
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions

Canonical Wnt/β-catenin signaling has central roles in development and diseases, and is initiated by the action of the frizzled (Fz) receptor, its coreceptor LDL receptor-related protein 6 (Lrp6), and the cytoplasmic dishevelled (Dvl) protein. The functional relationships among Fz, Lrp6 and Dvl have long been enigmatic. We demonstrated previously that Wnt-induced Lrp6 phosphorylation via glycogen synthase kinase 3 (Gsk3) initiates Wnt/β-catenin signaling. Here we show that both Fz and Dvl functions are critical for Wnt-induced Lrp6 phosphorylation through Fz-Lrp6 interaction. We also show that axin, a key scaffolding protein in the Wnt pathway, is required for Lrp6 phosphorylation via its ability to recruit Gsk3, and inhibition of Gsk3 at the plasma membrane blocks Wnt/β-catenin signaling. Our results suggest a model that upon Wnt-induced Fz-Lrp6 complex formation, Fz recruitment of Dvl in turn recruits the axin-Gsk3 complex, thereby promoting Lrp6 phosphorylation to initiate β-catenin signaling. We discuss the dual roles of the axin-Gsk3 complex and signal amplification by Lrp6-axin interaction during Wnt/β-catenin signaling.
The Two-Faced Potato Virus X: From Plant Pathogen to Smart Nanoparticle

Potato virus X (PVX) is a single-stranded RNA plant virus, historically investigated in light of the detrimental effects on potato, the world’s fourth most important food commodity. The study of the interactions with cells, and more generally with the plant, both locally and systemically, significantly contributed to unveil the mechanisms underlying gene silencing, fundamental not only in plant virology but also in the study of gene expression regulation. Unraveling the molecular events of PVX infection paved the way for the development of different viral expression vectors and consequential applications in functional genomics and in the biosynthesis of heterologous proteins in plants. Apart from that, the ease of manipulation and the knowledge of the virus structure (particle dimensions, shape and physicochemical features) are inspiring novel applications, mainly focused on nanobiotechnology. This review will lead the reader in this area, spanning from fundamental to applied research, embracing fields from plant pathology to vaccine and drug-targeted delivery, imaging and material sciences. Due to the versatile moods, PVX holds promise to become an interesting nanomaterial, in view to create the widest possible arsenal of new “bio-inspired” devices to face evolving issues in biomedicine and beyond.
The effect of nonsteroidal antiinflammatory drugs on electrolyte homeostasis and blood pressure in young and elderly persons with and without renal insufficiency.

Abstract The study objective was to determine the acute and long-term effects ofnonsteroidal antiinflammatory drugs (NSAIDs) on the excretion of sodium and potassium, blood pressure, and body weight in young and elderly persons without renal insufficiency, and in elderly persons with moderate renal insufficiency. We conducted a randomized, open-label, three-way, crossover study in which subjects were administered 800, mg ibuprofen three times daily, 20 mg piroxicam daily, and 200 mg sulindac twice daily. Measurements included clearance and balance studies of the excretion of sodium and potassium during a 24- hour period, sitting systolic and diastolic blood pressures, and body weight measurements. Ibuprofen, piroxicam, and sulindac reduced excretion of sodium and potassium. Maximum decrements in the fractional excretion of sodium and potassium were significant for all NSAIDs in each group (P
Type 3 peptide deformylases are required for oxidative phosphorylation in Trypanosoma brucei

Peptide deformylase (PDF) catalyses the removal of the formyl group from the first methionine of nascent proteins. Type 1 PDFs are found in bacteria and have orthologues in most eukaryotes. Type 2 PDFs are restricted to bacteria. Type 3 enzymes are found in Archaea and trypanosomatids and have not been studied experimentally yet. Thus, TbPDF1 and TbPDF2, the two PDF orthologues of the parasitic protozoa Trypanosoma brucei, are of type 3. An experimental analysis of these enzymes shows that both are mitochondrially localized, but that only TbPDF1 is essential for normal growth. Recombinant TbPDF1 exhibits PDF activity with a substrate specificity identical to that of bacterial enzymes. Consistent with these results, TbPDF1 is required for oxidative but not for mitochondrial substrate‐level phosphorylation. Ablation of TbPDF2, in contrast, does neither affect growth on standard medium nor oxidative phosphorylation. However, a reduced level of TbPDF2 slows down growth in a medium that selects for highly efficient oxidative phosphorylation. Furthermore, combined ablation of TbPDF1 and TbPDF2 results in an earlier growth arrest than is observed by downregulation of TbPDF1 alone. These results suggest that TbPDF2 is functionally linked to TbPDF1, and that it can influence the efficiency of oxidative phosphorylation.
Subclinical hypothyroidism and risk for incident ischemic stroke among postmenopausal women.

BACKGROUND Subclinical hypothyroidism (SCH) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function. However, the direct relationship of SCH with subsequent stroke is poorly studied. METHODS In this nested case-cohort study, we prospectively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women's Health Initiative Observational Study. Trained Women's Health Initiative staff, masked to thyroid status, adjudicated stroke cases. We assessed thyroid function using baseline blood specimens. Women with normal free thyroxine levels and thyrotropin (TSH) levels ≥4.69 mU/L were considered to have SCH. Primary analysis included 639 ischemic stroke cases and 2927 randomly selected subcohort members with an average of seven years of follow-up. RESULTS The multivariable adjusted hazard ratios (HR) from weighted Cox models were 1.06 (95% confidence interval [CI]: 0.77, 1.46) and 0.99 (95% CI: 0.67, 1.47) for women with any SCH and with mild SCH (TSH 4.69 to 6.99 mU/L), when compared with women with normal thyroid function. The HR for moderate/severe SCH (TSH ≥7.00 mU/L) was modestly elevated (HR: 1.22; 95% CI: 0.73, 2.05). CONCLUSIONS We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women.
The laboratory diagnosis of urinary tract infection

Urinarytract infection is common, and it is not surprising that urine specimens make up a large proportion of those samples submitted to the routine diagnostic laboratory. Many of these specimens will show no evidence of infection and several methods can be used to screen out negative samples. Those that grow bacteria need to be carefully assessed to quantify the degree of bacteriuria and hence clinical relevance. To inﬂuence treatment, a ﬁnal report should be produced within 24 hours of specimen re-ceipt, with turnaround times continuously monitored. Much work needs to be done to determine the cost e V ectiveness involved in processing urine specimens and the evidence base for the ﬁnal report provided. ( J Clin Pathol 2001; 54 :911–919)
Thromboxane A 2 and Prostacyclin Biosynthesis in Children and Adolescents With Pulmonary Vascular Disease

Background. The pathogenesis of pulmonary vascular disease in children with congenital heart disease is incompletely understood. Thromboxane (TX) A2 and prostacyclin (PGI2) have opposing effects on platelet aggregation and pulmonary vascular smooth muscle. An imbalance in their biosynthesis could contribute to the progressive increase in pulmonary vascular resistance seen in older untreated patients with pulmonary hypertensive congenital heart disease and the thrombotic complications they may develop. Methods and Results. We investigated TXA2 and PGI2 biosynthesis in 15 young children (0.2 to 2.25 years old) with congenital heart disease with increased pulmonary blood flow and potentially reversible pulmonary vascular disease by measuring urinary excretion of 2,3-dinor-TXB2 and 2,3-dinor-6-oxoprostaglandin (PG) Fa, and compared the findings with those in 16 healthy children (0.5 to 2.8 years old). 2,3-Dinor-TXB2 excretion was greater in the patients than in control subjects (1253±161 versus 592± 122 ng/g creatinine; P<.001). Excretion of 2,3-dinor-6-oxo-PGF,, was 452±54 compared with 589±95 ng/g creatinine in control subjects. In 5 patients who underwent successful cardiac surgery >1 year later excretion of 2,3-dinor-TXB2 decreased from 1100±298 to 609±131 ng/g creatinine (P<.05), a value comparable to those in 5 healthy children of similar age (749±226 ng/g creatinine). We also compared 15 patients (11 to 23 years old) with advanced irreversible pulmonary vascular disease with 19 healthy control subjects (10 to 23 years old). The ratio of TX to PGI2 metabolite excretion was greater in the patients than in control subjects (3.5±0.6 versus 2.0±0.3; P<.05). Conclusions. There is increased 2,3-dinor-TXB2 excretion in children with congenital heart disease and
Distance functions and geodesics on points clouds

Abstract : An algorithm for computing intrinsic distance functions and geodesics on sub-manifolds vector r(sup d) given by point clouds is introduced in this paper. The basic idea is that, as shown in this paper intrinsic distance functions and geodesics on general co-dimension sub-manifolds vector r(sup d) can be accurately approximated by the extrinsic Euclidean ones computed in a thin offset band surrounding the manifold. This permits the use of computationally optimal algorithms for computing distance functions in Cartesian grids. We then use these algorithms, modified to deal with spaces with boundaries, and obtain also for the case of intrinsic distance functions on sub-manifolds of vector r(sup d), a computationally optimal approach. For point clouds. the offset band is constructed without the need to explicitly find the underlying manifold, thereby computing intrinsic distance functions and geodesics on point clouds while skipping the manifold reconstruction step. The case of point clouds representing noisy samples of a sub-manifold of Euclidean space is studied as well. All the underlying theoretical results are presented. together with experimental examples, and comparisons to graph-based distance algorithms.
Durability of Pultruded E-Glass/Vinylester under Combined Hygrothermal Exposure and Sustained Bending

The effect of combined water immersion and sustained bending on the degradation response of E-glass/vinylester composites is characterized through mechanical testing (tension and short-beam-shear) and moisture uptake. It is seen that moisture uptake and coefficient of diffusion increase with levels of sustained strain and that uptake characteristics can be predicted with a reasonable level of accuracy using a model incorporating the free volume approach. Both tensile strength and short-beam-shear strength decrease with increasing periods of immersion and level of sustained strain. A transition in degradative response can be identified in terms of level of sustained strain. Comparisons of response with ACI-440 guidelines indicate that the use of stress limitations is essential in specifying design allowables since the use of ACI thresholds involving environmental exposure factors alone may be unconservative for long periods of service. It is emphasized that synergistic effects of sustained bending and water immersion are accelerative and that further research is needed on ascertaining the safe level of sustained loading for use in civil infrastructure.
Free-Riding and Competition in Network Markets for Digital Goods

We present a continuous, stochastic model - the first of its kind - for the monetary flow in multi-level markets allowing for the quantitative assessment of the incentive accruing to market participants through resales revenues. The main application of the model is for novel business models for the marketing of information goods, which purport to yield alternatives to technical copyright protection and DRM. We show analytically that within the scope of the model free-riding can be mitigated by employing multi-level marketing, and that multi-level markets are open markets for competing information goods.