Miracle-dz/UniFAR-FTUs huggingface dataset:
Individualised prediction of alternate-day aspirin treatment effects on the combined risk of cancer, cardiovascular disease and gastrointestinal bleeding in healthy women

Background The value of aspirin in primary prevention of cancer and cardiovascular disease (CVD) remains unclear. The aim of this study was to identify women who benefit from alternate-day aspirin with regard to all relevant outcomes, including cancer, CVD and major gastrointestinal bleeding. Methods Long term follow-up data of 27 939 healthy women with baseline plasma samples in the Women's Health Study, a randomised trial of 100 mg alternate-day aspirin versus placebo, were used to develop competing risks models for individualised prediction of absolute risk reduction of the combination of CVD, cancer and major gastrointestinal bleeding by aspirin. Results Although aspirin was associated with a modestly decreased 15-year risk of colorectal cancer, CVD, and in some women non-colorectal cancer, aspirin treatment resulted in a negative treatment effect in the majority of women if gastrointestinal bleeding was also taken into account. The excess risk of major gastrointestinal bleeding by aspirin increased with age, but the benefits for colorectal cancer and CVD risk were also greater at higher age. Decision curves indicated that selective treatment of women ≥65 years may improve net benefit compared to treating all, none and prediction-based treatment. The observed 15-year number needed to treat to prevent one event among women ≥65 years was 29 (95% CI 12 to 102). Conclusions Concurrent evaluation of the absolute effects on cancer, CVD and major gastrointestinal bleeding showed that alternate-day use of low-dose aspirin is ineffective or harmful in the majority of women in primary prevention. Selective treatment of women ≥65 years with aspirin may improve net benefit. Trial registration number NCT00000479.
Mass spectrometry for serine ADP-ribosylation? Think o-glycosylation!

Abstract Protein ADP-ribosylation (ADPr), a biologically and clinically important post-translational modification, exerts its functions by targeting a variety of different amino acids. Its repertoire recently expanded to include serine ADPr, which is emerging as an important and widespread signal in the DNA damage response. Chemically, serine ADPr (and more generally o-glycosidic ADPr) is a form of o-glycosylation, and its extreme lability renders it practically invisible to standard mass spectrometry approaches, often leading to erroneous localizations. The knowledge from the mature field of o-glycosation and our own initial difficulties with mass spectrometric analyzes of serine ADPr suggest how to avoid these misidentifications and fully explore the scope of o-glycosidic ADPr in DNA damage response and beyond.
An Investigative Study into Psychological and Fertility Sequelae of Gestational Trophoblastic Disease: The Impact on Patients’ Perceived Fertility, Anxiety and Depression

Objectives Gestational Trophoblastic Disease (GTD) comprises a group of disorders that derive from the placenta. Even if full recovery is generally expected, women diagnosed with GTD have to confront: the loss of a pregnancy, a potentially life-threatening diagnosis and delays in future pregnancies. The aim of the study is to evaluate the psychological impact of GTD, focusing on perceived fertility, depression and anxiety. Methods 37 patients treated for GTD at San Raffaele Hospital, Milan, took part in the study. The STAI-Y (State-Trait Anxiety Inventory), the BDI-SF (Beck Depression Scale-Short Form) and the FPI (Fertility Problem Inventory) were used. Patients were grouped on the basis of presence of children (with or without), age (< or ≥35) and type of diagnosis (Hydatidiform Mole, HM, or Gestational Trophoblastic Neoplasia, GTN). Differences in the values between variables were assessed by a t-type test statistic. Three-way ANOVAs were also carried out considering the same block factors. Results The study highlights that women suffering from GTN had higher depression scores compared to women suffering from HM. A significant correlation was found between anxiety (state and trait) and depression. Younger women presented higher Global Stress scores on the FPI, especially tied to Need for Parenthood and Relationship Concern subscales. Need for Parenthood mean scores significantly varied between women with and without children too. Conclusions We can conclude that fertility perception seems to be negatively affected by GTD diagnosis, particularly in younger women and in those without children. Patients should be followed by a multidisciplinary team so as to be supported in the disease’s psychological aspects too.
On the Equivalence between the Primal-Dual Schema and the Local Ratio Technique

We discuss two approximation approaches, the primal-dual schema and the local-ratio technique.W e present two relatively simple frameworks, one for each approach, which extend known frameworks for covering problems. We show that the two are equivalent, and conclude that the integrality gap of an integer program serves as a bound to the approximation ratio when working with the local-ratio technique.
INFLUENCE OF ACETAZOLAMIDE ON AQP1 GENE EXPRESSION IN TESTIS AND ON SPERM COUNT/MOTILITY IN EPIDIDYMIS OF RATS

Acetazolamide (Ace) is a putative inhibitor of carbonic anhydrase (CA), an enzyme that catalyzes the equilibration of carbon dioxide and carbonic acid and plays a key role in HCO 3 - and water reabsorption and acid secretion. Aquaporins (AQPs) are channel-forming membrane glycoproteins that mediate water reabsorption by the renal tubules and other organs of mammals. AQP1 and CAII or CAIV share many common biological properties. Previous studies have shown that AQP1 and CA are located at the same sites in cells of the male reproductive tract. In the present study, Ace at a dose of 40 mg/kg/d 2 14, administered per os, suppressed AQP1 gene expression and inhibited CA activity in rat testis. On day 7 of treatment the epididymal sperm motility was significantly reduced, while on day 14 a decrease in sperm count occurred. Ace caused a marked downregulation of AQP1 gene expression; significant suppression occurred on days 7 and 14. Moreover, CA activity was totally blocked throughout the treatment period. The present findings suggest that the reduction of rat sperm motility and count by Ace can be attributed to its capacity to downregulate AQP1 water channel gene expression.
Atrio-Esophageal Fistula as a Complication of Percutaneous Transcatheter Ablation of Atrial Fibrillation

Background—Radiofrequency ablation for atrial fibrillation is becoming widely practiced. Methods and Results—Two patients undergoing circumferential pulmonary vein ablation for atrial fibrillation in different centers developed symptoms compatible with endocarditis 3 to 5 days after the procedure. Their clinical condition deteriorated rapidly, and both suffered multiple gaseous and/or septic embolic events causing cerebral and myocardial damage. One patient survived after emergency cardiac and esophageal surgery; the other died of extensive systemic embolization. An atrio-esophageal fistula was identified in both patients. Conclusions—Atrio-esophageal fistulas can occur after catheter ablation in the posterior wall of the left atrium. This diagnosis should be excluded in any patient with symptoms or signs of endocarditis after left atrial ablation, and expeditious cardiac surgery is critical if the diagnosis is confirmed. Lower power and temperature settings for applications of radiofrequency energy along the posterior left atrial wall may prevent further cases of fistula formation.
Effects of cyanobacterial toxicity and morphology on the population growth of freshwater zooplankton: Meta‐analyses of laboratory experiments

We synthesized data from 66 published laboratory studies, representing 597 experimental comparisons, examining the effects of cyanobacterial toxicity and morphology on the population growth rate and survivorship of 17 genera (34 species) of freshwater, herbivorous zooplankton. Two meta‐analyses were conducted with these data. The primary analysis compared herbivore population growth rates for grazers fed treatment diets containing cyanobacteria versus control diets comprising phytoplankton that are generally considered to be nutritious for zooplankton (chlorophytes and/or flagellates). This analysis confirmed that cyanobacteria were poor foods relative to small chlorophytes and flagellates. More importantly, filamentous cyanobacteria were found to be significantly better foods for grazers than single‐celled cyanobacteria over all studies. Surprisingly, the presence or absence of commonly‐measured toxic compounds (microcystins in 70% of the cases) in the diet had no overall influence on grazer population growth relative to control diets. A secondary analysis compared survival rates for grazers fed cyanobacteria versus no food. In contrast to the primary analysis, grazer survival was more negatively affected by toxic cyanobacteria than non‐toxic cyanobacteria, relative to starvation. However, this difference was attributable to the effects of a single Microcystis strain, PCC7820. Thus, though some cyanobacterial strains appear to be toxic to some strains of zooplankton, the overall role of commonly‐assayed cyanobacterial toxins as a determinant of food quality may be less than widely assumed. We suggest that more attention be focused on nutritional deficiencies, morphology, and the toxicity of undescribed cyanobacterial compounds as mediators of the poor food quality of cyanobacteria for zooplankton.
Battling Bad Bits with Checksums in the Loris Page Cache

In this paper, we aim to improve the reliability of a central part of the operating system storage stack: the page cache. We consider two reliability threats: memory errors, where bits in DRAM are flipped due to cosmic rays, and software bugs, where programming errors may ultimately result in data corruption and crashes. We argue that by making use of checksums, we can significantly reduce the probability that either threat results in any application-visible effects. In particular, we can use checksums to detect memory corruption as well as validate the integrity of the cache's internal state for recovery after a crash. We show that in many cases, we can avoid the overhead of computing checksums especially for these purposes. We implement our ideas in the Loris storage stack. Our analysis and evaluation show that our approach improves the overall reliability of the cache at relatively little added cost.
The Formation of DNA Sugar Radicals from Photoexcitation of Guanine Cation Radicals

Abstract Shukla, L. I. , Pazdro, R. , Huang, J., DeVreugd, C. , Becker, D. and Sevilla, M. D. The Formation of DNA Sugar Radicals from Photoexcitation of Guanine Cation Radicals. Radiat. Res. 161, 582–590 (2004). In this investigation of radical formation and reaction in γ- irradiated DNA and model compounds, we report the conversion of the guanine cation radical (one-electron oxidized guanine, G·+) to the C1′ sugar radical and another sugar radical at the C3′ or C4′ position (designated C3′·/C4′·) by visible and UV photolysis. Electron spin resonance (ESR) spectroscopic investigations were performed on salmon testes DNA as well as 5′-dGMP, 3′-dGMP, 2′-deoxyguanosine and other nucleosides/nucleotides as model systems. DNA samples (25– 150 mg/ml D2O) were prepared with Tl3+ or Fe(CN)3−6 as electron scavengers. Upon γ irradiation of such samples at 77 K, the electron-gain path in the DNA is strongly suppressed and predominantly G·+ is found; after UV or visible photolysis, the fraction of the C1′ sugar radical increases with a concomitant reduction in the fraction of G·+. In model systems, 3′- dGMP+·; and 5′-dGMP+· were produced by attack of Cl·−2 on the parent nucleotide in 7 M LiCl glass. Subsequent visible photolysis of the 3′-dGMP+· (77 K) results predominantly in formation of C1′· whereas photolysis of 5′-dGMP+· results predominantly in formation of C3′·/C4′·. We propose that sugar radical formation is a result of delocalization of the hole in the electronically excited base cation radical into the sugar ring, followed by deprotonation at specific sites on the sugar.
Metabolomics of Plasma in XLH Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms

X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; p = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, p = 0.01). A total of 106 metabolites were identified. Acetylcarnitine (p = 0.03), pyruvate p = (0.04), ethanolamine (p = 0.03), and butyric acid (p = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.
The myosin filament

Different multistage fixation procedures patterned after the procedure described by Reedy (1976) have been evaluated with regard to preservation of subfllament structural organization along the length of the vertebrate skeletal myosin filament. The criteria used for evaluation of structural preservation include (a) the precision of subfllament organization as reflected by the quality of the optical diffraction patterns obtained from images of transverse sections of the myosin filament and (b) the clarity with which structural differences in serial transverse sections along the myosin filament could be defined.
Natural deictic communication with humanoid robots

A simple view of deictic communication only includes the indication process and recognition process: a person points at an object and says something about it such as "look at this," and then the other person recognizes the pointing gesture and pays attention to the indicated object. However, this simple view lacks three important processes: attention synchronization, context focus, and believability establishment. We refer to these three processes as "facilitation processes" and implement them in a humanoid robot with a motion capturing system. An experiment with 30 subjects revealed that the facilitation processes make deictic communication natural.
Fatigue in multiple sclerosis: relation to depression, physical impairment, personality and action control

Athough fatigue is one of the most common symptoms of multiple sclerosis, it is yet poorly understood and therefore difficult to manage. To clarify the nature of fatigue we investigated its relationship to depression, physical impairment, personality and action control and compared these variables between a sample of 41 MS patients and 41 healthy controls. Physical impairment was assessed by the EDSS and all other dimensions, using questionnaires. Stepwise linear regression analyses revealed that physical impairment was related to physical fatigue in MS patients. Depression was the main factor influencing fatigue among both, MS patients and controls. What clearly differentiated the two groups was the correlation between fatigue and action control. Decreased levels of action control imply attentional and motivational deficits and were only found in fatigued MS patients. Our study indicates that motivational disturbances might be specific for MS related fatigue. Multiple Sclerosis 2007; 13: 1161—1167. http://msj.sagepub. com
On selfish routing in Internet-like environments

A recent trend in routing research is to avoid inefficiencies in network-level routing by allowing hosts to either choose routes themselves (e.g., source routing) or use overlay routing networks (e.g., Detour or RON). Such approaches result in selfish routing, because routing decisions are no longer based on system-wide criteria but are instead designed to optimize host-based or overlay-based metrics. A series of theoretical results showing that selfish routing can result in suboptimal system behavior have cast doubts on this approach. In this paper, we use a game-theoretic approach to investigate the performance of selfish routing in Internet-like environments based on realistic topologies and traffic demands in our simulations. We show that in contrast to theoretical worst cases, selfish routing achieves close to optimal average latency in such environments. However, such performance benefits come at the expense of significantly increased congestion on certain links. Moreover, the adaptive nature of selfish overlays can significantly reduce the effectiveness of traffic engineering by making network traffic less predictable
Feedback Capacity of Gaussian Channels Revisited

In this paper, we revisit the problem of finding the average capacity of the Gaussian feedback channel. First, we consider the problem of finding the average capacity of the analog Gaussian noise channel, where the noise has an arbitrary spectral density. We introduce a new approach to the problem, where we solve the problem over a finite number of transmissions and then consider the limit of an infinite number of transmissions. Furthermore, we consider the important special case of stationary Gaussian noise with finite memory. We show that the channel capacity at stationarity can be found by solving a semi-definite program, and hence computationally tractable. We also give new proofs and results of the non-stationary solution which bridges the gap between results in the literature for the stationary and non-stationary feedback channel capacities. It is shown that a linear communication feedback strategy is optimal. Similar to the solution of the stationary problem, it is shown that the optimal linear strategy is to transmit a linear combination of the information symbols to be communicated and the innovations for the estimation error of the state of the noise process.
The concentration and persistence in the level of health expenditures over time: Estimates for the U.S. population, 2006-2007

Estimates of the health care expenses of the U.S. civilian noninstitutionalized (community) population are critical to policymakers and others concerned with access to medical care and the cost and sources of payment for that care. In 2007, health care expenses among the U.S. community population totaled $1.13 trillion. Medical care expenses, however, are highly concentrated among a relatively small proportion of individuals in the community population. As previously reported in 1996, the top 1 percent of the U.S. population accounted for 28 percent of the total health care expenditures and the top 5 percent for more than half. More recent data have revealed that over time there has been some decrease in the extent of this concentration at the upper tail of the expenditure distribution (Yu and EzzatiRice, 2005).
Editorial: What can simple brains teach us about how vision works

Vision is the process of extracting behaviorally-relevant information from patterns of light that fall on retina as the eyes sample the outside world. Traditionally, non-human primates have been viewed by many as the animal model-of-choice for investigating the neuronal substrates of visual processing, not only because their visual systems closely mirror our own (e.g., Orban, 2008; Nassi and Callaway, 2009 for a review), but also because it is often assumed that “simpler” brains lack advanced visual processing machinery. However, this narrow view of visual neuroscience ignores the fact that vision is widely distributed throughout the animal kingdom, enabling a wide repertoire of complex behaviors in species from insects to birds, fish, and mammals. Recent years have seen a resurgence of interest in alternative animal models for vision research, such as rodents (see Huberman and Niell, 2011; Zoccolan, 2015 for a review). This resurgence is partly due to the availability of increasingly powerful experimental approaches (e.g., optogenetics and two-photon imaging) that are challenging to apply to their full potential in primates. Meanwhile, even more phylogenetically distant species such as birds, fish, and insects have long been workhorse animal models for gaining insight into the core computations underlying visual processing (see Baier, 2000; Bilotta and Saszik, 2001; Borst et al., 2010; Aptekar and Frye, 2013 for a review). In many cases, these animal models are valuable precisely because their visual systems are simpler than the primate visual system. Simpler systems are often easier to understand, and studying a diversity of neuronal systems that achieve similar functions can focus attention on those computational principles that are universal and essential. This Research Topic provides a survey of the state of the art in the use of non-primate models of visual functions. It includes original research, methods articles, reviews, and opinions that exploit a variety of animal models (including rodents, birds, fishes and insects) to investigate visual function. The experimental approaches covered by these studies range from psychophysics and electrophysiology to histology and genetics, testifying to the richness and depth of visual neuroscience in non-primate species. Below, we briefly summarize the contributions to this Research Topic.
Optimisation mechanism for web search results using topic knowledge

Web searching - one of the most frequent activities in the internet community - is perhaps the most complicated one because of the abundant resulting information available. Users are often puzzled because of long results of ranking lists that are compiled without considering their individual preferences and needs. We present a mechanism in this work that reranks and groups search results on the user's side according to his/her explicit and implicit choices. Furthermore, a caching strategy is introduced to minimise personalisation effect response time. A web environment prototype has been developed to exemplify the potentials of the proposed mechanism. User assessment has been conducted to verify the effectiveness of the mechanism. Results and feedbacks have been efficient and encouraging, respectively.