Miracle-dz/UniFAR-FTUs huggingface dataset:
Ankylosing Spondylitis Is Associated With an Increased Risk of Vertebral and Nonvertebral Clinical Fractures: A Population‐Based Cohort Study

The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population‐based public health database in Spain, Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age‐matched, gender‐matched, and general practice surgery–matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls (n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti‐inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown. © 2014 American Society for Bone and Mineral Research
Serum Response Factor Mediated Gene Activity in Physiological and Pathological Processes of Neuronal Motility

In recent years, the transcription factor serum response factor (SRF) was shown to contribute to various physiological processes linked to neuronal motility. The latter include cell migration, axon guidance, and, e.g., synapse function relying on cytoskeletal dynamics, neurite outgrowth, axonal and dendritic differentiation, growth cone motility, and neurite branching. SRF teams up with myocardin related transcription factors (MRTFs) and ternary complex factors (TCFs) to mediate cellular actin cytoskeletal dynamics and the immediate-early gene (IEG) response, a bona fide indicator of neuronal activation. Herein, I will discuss how SRF and cofactors might modulate physiological processes of neuronal motility. Further, potential mechanisms engaged by neurite growth promoting molecules and axon guidance cues to target SRF’s transcriptional machinery in physiological neuronal motility will be presented. Of note, altered cytoskeletal dynamics and rapid initiation of an IEG response are a hallmark of injured neurons in various neurological disorders. Thus, SRF and its MRTF and TCF cofactors might emerge as a novel trio modulating peripheral and central axon regeneration.
A diary study of work-related reading: design implications for digital reading devices

In this paper we describe a diary study of how people read in the course of their daily working lives. Fifteen people from a wide variety of professions were asked to log their daily document activity for a period of 5 consecutive working days. Using structured interviews, we analysed their reading activities in detail. We examine the range of reading activities that our subjects carried out, and then present findings relating to both common characteristics and variation across the sample. From these findings, we discuss some implications for the design of digital readiig devices.
Self-Reported Migraine and Chronic Fatigue Syndrome Are More Prevalent in People with Myofascial vs Nonmyofascial Temporomandibular Disorders.

AIMS To compare the number of comorbidities and the prevalence of five specific comorbidities in people who have temporomandibular disorders (TMD) with or without myofascial pain. METHODS This cross-sectional study included 180 patients seeking TMD treatment in Boston and Montreal hospitals. A self-administered questionnaire was used to collect information on sociodemographic and behavioral factors, as well as the presence of the following five comorbidities: migraine, chronic fatigue syndrome, irritable bowel syndrome, interstitial cystitis, and restless leg syndrome. TMD was diagnosed using the Research Diagnostic Criteria for TMD. Chi-square and Student t tests were used for categorical and continuous variables, respectively, to test for differences between myofascial (n = 121) and nonmyofascial (n = 59) TMD groups. Multiple logistic regression analysis was used to compare the type and number of self-reported comorbidities in both groups, controlling for confounding variables. RESULTS The following were found to be significantly higher in the myofascial TMD group than in the nonmyofascial TMD group: self-reported migraine (55% vs 28%, P = .001), chronic fatigue syndrome (19% vs 5%, P = .01), and the mean total number of comorbidities (1.30 vs 0.83, P = .01). CONCLUSION Individuals with myofascial TMD had a higher prevalence of self-reported migraine and chronic fatigue syndrome than those with nonmyofascial TMD.
Unsupervised Learning of Fuzzy Association Rules for Consumer Behavior Modeling

Marketing-oriented firms are especially concerned with modeling consumer behavior to improve their information and aid their decision processes on markets. For this purpose, marketing experts use complex models and apply statistical methodologies to infer conclusions from data. Recently, the application of machine learning has been detected as a promising approach to complement these classical techniques of analysis. In this paper, we follow this idea and propose a system, addressed as Fuzzy-CSar, to extract fuzzy association rules from certain consumption problem analyzed. But, as a differentiating sign of identity from other methods, Fuzzy-CSar does not assume any aprioristic causality (so model) within the variables forming the consumer database. Instead, the system is responsible for extracting the strongest associations among variables, and so, the structure of the problem. Fuzzy-CSar is applied to a real-world marketing problem and the results are compared with those obtained by a multi-objective genetic fuzzy system expressly designed for this marketing problem. The results show the advantages of evolving fuzzy association rules and the competitiveness of Fuzzy-CSar in general.
The p53 activation domain binds the TATA box-binding polypeptide in Holo-TFIID, and a neighboring p53 domain inhibits transcription

Antioncogene product p53 is a transcriptional transactivator. To investigate how p53 stimulates transcription, we examined the interaction of p53 with general transcription factors in vitro. We found that p53 binds directly to the human TATA box-binding polypeptide (TBP). We also observed a direct interaction between p53 and purified holo-TFIID, a complex composed of TBP and a group of TBP-associated polypeptides known as TAFs. The p53 binding domain on TBP was mapped to the conserved region of TBP, including residues 220 to 271. The TBP binding domain on p53 was mapped to the p53 activation domain between residues 20 and 57. To analyze the significance of the p53-TBP interaction in p53 transactivation, we compared the ability of Gal4-p53 fusion proteins to bind to TBP in vitro and to activate transcription in transient transfection assays. Fusion proteins which bound to TBP activated transcription, and those that did not bind to TBP did not activate transcription to a detectable level, suggesting that a direct interaction between TBP and p53 is required for p53 transactivation. We also found that inclusion of residues 93 to 160 of p53 in a Gal4-p53 fusion repressed transcriptional activation 100-fold. Consequently, this region of p53 inhibits transcriptional activation by the minimal p53 activation domain. Highest levels of activation were observed with sequences 1 to 92 of p53 fused to Gal4, even though this construct bound to TBP in vitro with an affinity similar to that of other Gal4-p53 fusion proteins. We conclude that TBP binding is necessary for p53 transcriptional activation and that p53 sequences outside the TBP binding domain modulate the level of activation.
Regularization of Case-Specific Parameters for Robustness and Efficiency

Regularization methods allow one to handle a variety of inferential problems where there are more covariates than cases. This allows one to consider a potentially enormous number of covariates for a problem. We exploit the power of these techniques, supersaturating models by augmenting the "natural" covariates in the problem with an additional indicator for each case in the data set. We attach a penalty term for these case-specific indicators which is designed to produce a desired effect. For regression methods with squared error loss, an $\ell_1$ penalty produces a regression which is robust to outliers and high leverage cases; for quantile regression methods, an $\ell_2$ penalty decreases the variance of the fit enough to overcome an increase in bias. The paradigm thus allows us to robustify procedures which lack robustness and to increase the efficiency of procedures which are robust. We provide a general framework for the inclusion of case-specific parameters in regularization problems, describing the impact on the effective loss for a variety of regression and classification problems. We outline a computational strategy by which existing software can be modified to solve the augmented regularization problem, providing conditions under which such modification will converge to the optimum solution. We illustrate the benefits of including case-specific parameters in the context of mean regression and quantile regression through analysis of NHANES and linguistic data sets.
Lazy call-by-value evaluation

Designing debugging tools for lazy functional programming languages is a complex task which is often solved by expensive tracing of lazy computations. We present a new approach in which the information collected as a trace is reduced considerably (kilobytes instead of megabytes). The idea is to collect a kind of step information for a call-by-value interpreter, which can then efficiently reconstruct the computation for debugging/viewing tools, like declarative debugging. We show the correctness of the approach, discuss a proof-of-concept implementation with a declarative debugger as back end and present some benchmarks comparing our new approach with the Haskell debugger Hat.
The ventral tegmental area revisited: is there an electrophysiological marker for dopaminergic neurons?

The ventral tegmental area (VTA) and in particular VTA dopamine (DA) neurons are postulated to play a central role in reward, motivation and drug addiction. However, most evidence implicating VTA DA neurons in these functions is based on indirect electrophysiological characterization, rather than cytochemical identification. These physiological criteria were first established in the substantia nigra pars compacta (SNc), but their validity in the VTA is uncertain. In the current study we found that while 88 ± 2% of SNc neurons labelled by the neuronal marker NeuN were co‐labelled for the catecholamine enzyme tyrosine hydroxylase (TH), a much smaller percentage (55 ± 2%) of VTA neurons co‐expressed TH. In addition, using in vitro whole‐cell recordings we found that widely accepted physiological criteria for VTA DA neurons, including the hyperpolarization‐activated inwardly rectifying non‐specific cation current (Ih), spike duration, and inhibition by DA D2 receptor agonists, do not reliably predict the DA content of VTA neurons. We could not distinguish DA neurons from other VTA neurons by size, shape, input resistance, Ih size, or spontaneous firing rate. Although the absence of an Ih reliably predicted that a VTA neuron was non‐dopaminergic, and Ih(−) neurons differ from Ih(+) neurons in firing rate, interspike interval (ISI) standard deviation, and ISI skew, no physiological property examined here is both sensitive and selective for DA neurons in the VTA. We conclude that reliable physiological criteria for VTA DA neuron identification have yet to be determined, and that the criteria currently being used are unreliable.
Prognostic and predictive factors in primary breast cancer and their role in patient management: The Nottingham Breast Team.

Breast cancer is the most common carcinoma amongst women in the Western world, yet there are now encouraging signs that improvements in mortality may be a realistic target. Increasing breast awareness amongst women due to better health education can lead to earlier clinical detection. In addition, population screening with mammography can achieve a significant improvement in survival. With significant changes in the range and type of therapeutic options available for patients with breast cancer, there is now a trend towards patients exercising their right in management and therapeutic decisions. All these developments highlight the increasing importance of prognostic and predictive factors in the management of patients with breast cancer. In this review we will discuss current prognostic and predictive factors with particular emphasis on those of relevance in routine histopathology, especially with respect to their clinical applications.
Traditional eye medication and pterygium occurrence in Limpopo Province.

BACKGROUND The relative importance of environmental and hereditary factors in the occurrence of pterygium in African blacks has not been reported. AIM To investigate the relative significance of factors associated with pterygium occurrence. METHODS This was a prospective case-controlled study where 150 pterygium patients and 150 controls participated. Interviews were conducted, eyes examined and multivariate analysis done. The families of 51 pterygium cases and 50 controls were examined for presence of pterygium. RESULTS Of 150 cases and 150 controls, 79 (52.6%) and 60 (40%) used traditional eye drops (odds ratio (OR) 2.03; p=0.009. Ten cases (6.6%) and 26 controls (17.3%) had unstable tear film (OR 0.30; p=0.007. Forty-six cases (30.6%) and 15 controls (10%) reported a positive family history (OR 3.93; p<0.001). Groups of 3 - 5 pterygium cases in a household occurred in 36 of 51 pterygium families (70.5%) v. 1 of 50 controls (2%). CONCLUSIONS Pterygium occurrence was associated with the use of traditional eye drops, a positive family history and having groups of diagnosed pterygium-affected relatives. However, unstable tear film seemed protective against pterygium occurrence.
Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation.
Interactive Pen-and-Ink Illustration

We present an interactive system for creating pen-and-ink illustrations. The system uses stroke textures-collections of strokes arranged in different patterns-to generate texture and tone. The user "paints" with a desired stroke texture to achieve a desired tone, and the computer draws all of the individual strokes. We present an interactive system for creating pen-and-ink illustrations. The system uses stroke textures-collections of strokes arranged in different patterns-to generate texture and tone. The user "paints" with a desired stroke texture to achieve a desired tone, and the computer draws all of the individual strokes. By removing the burden of placing individual strokes from the user, the illustration system makes it possible to create fine stroke work with a purely mouse-based interface. Thus, this approach holds promise for bringing high-quality black-and-white illustration to the world of personal computing and desktop publishing.
Comparison of Listing Strategies for Allosensitized Heart Transplant Candidates Requiring Transplant at High Urgency: A Decision Model Analysis

Allosensitized children who require a negative prospective crossmatch have a high risk of death awaiting heart transplantation. Accepting the first suitable organ offer, regardless of the possibility of a positive crossmatch, would improve waitlist outcomes but it is unclear whether it would result in improved survival at all times after listing, including posttransplant. We created a Markov decision model to compare survival after listing with a requirement for a negative prospective donor cell crossmatch (WAIT) versus acceptance of the first suitable offer (TAKE). Model parameters were derived from registry data on status 1A (highest urgency) pediatric heart transplant listings. We assumed no possibility of a positive crossmatch in the WAIT strategy and a base‐case probability of a positive crossmatch in the TAKE strategy of 47%, as estimated from cohort data. Under base‐case assumptions, TAKE showed an incremental survival benefit of 1.4 years over WAIT. In multiple sensitivity analyses, including variation of the probability of a positive crossmatch from 10% to 100%, TAKE was consistently favored. While model input data were less well suited to comparing survival when awaiting transplantation across a negative virtual crossmatch, our analysis suggests that taking the first suitable organ offer under these circumstances is also favored.
No Evidence for an Item Limit in Change Detection

Change detection is a classic paradigm that has been used for decades to argue that working memory can hold no more than a fixed number of items (“item-limit models”). Recent findings force us to consider the alternative view that working memory is limited by the precision in stimulus encoding, with mean precision decreasing with increasing set size (“continuous-resource models”). Most previous studies that used the change detection paradigm have ignored effects of limited encoding precision by using highly discriminable stimuli and only large changes. We conducted two change detection experiments (orientation and color) in which change magnitudes were drawn from a wide range, including small changes. In a rigorous comparison of five models, we found no evidence of an item limit. Instead, human change detection performance was best explained by a continuous-resource model in which encoding precision is variable across items and trials even at a given set size. This model accounts for comparison errors in a principled, probabilistic manner. Our findings sharply challenge the theoretical basis for most neural studies of working memory capacity.
Physical activity and weight loss: does prescribing higher physical activity goals improve outcome?

BACKGROUND Recommending increased physical activity facilitates long-term weight loss, but the optimal level of physical activity to recommend is unknown. OBJECTIVE The objective of the study was to evaluate the efficacy for long-term weight loss of recommendations for much higher physical activity than those normally used in behavioral treatments. DESIGN Overweight men and women (n = 202) were randomly assigned to either a standard behavior therapy (SBT) for obesity, incorporating an energy expenditure (EE) goal of 1000 kcal/wk, or to a high physical activity (HPA) treatment, in which the goal was an EE of 2500 kcal/wk. To help HPA treatment group participants achieve this high exercise goal, their treatment included encouragement to recruit 1-3 exercise partners into the study, personal counseling from an exercise coach, and small monetary incentives. RESULTS The HPA treatment group reported achieving higher mean (+/- SD) physical activity levels than did the SBT group at 6 mo (EE of 2399 +/- 1571 kcal/wk compared with 1837 +/- 1431 kcal/wk), 12 mo (EE of 2249 +/- 1751 kcal/wk compared with 1565 +/- 1309 kcal/wk), and 18 mo (EE of 2317 +/- 1854 kcal/wk compared with 1629 +/- 1483 kcal/wk) (all P < 0.01). Mean (+/- SEM) cumulative weight losses at 6, 12, and 18 mo in the HPA treatment group were 9.0 +/- 7.1, 8.5 +/- 7.9, and 6.7 +/- 8.1 kg, respectively. In the SBT group, the corresponding weight losses were 8.1 +/- 7.4, 6.1 +/- 8.8, and 4.1 +/- 7.3 kg, respectively. Between-group differences in weight loss were significant at 12 and 18 mo. CONCLUSION These results suggest that recommendations of higher levels of physical activity (EE of 2500 kcal/wk) promote long-term weight loss better than do conventional recommendations.
Analysis of T-Wave Morphology From the 12-Lead Electrocardiogram for Prediction of Long-Term Prognosis in Male US Veterans

Background—The aim of the present study was to assess the prognostic value of novel repolarization descriptors from the 12-lead ECG in a large cohort of US veterans. Methods and Results—Male US veterans (n=813) with cardiovascular disease had digital 12-lead ECGs recorded at the VA Medical Center, Washington, DC, between 1984 and 1991. The patient series was retrospectively compiled in 1991; follow-up was prospectively assessed until 2000. Novel ECG variables characterizing repolarization and the T-wave loop were automatically analyzed. Of 772 patients with technically analyzable data, 252 patients (32.6%) died after a mean follow-up of 10.4±3.8 years. Direct comparison between dead and alive patients showed that the so-called T-wave residua (the absolute and relative amount of nondipolar contents within the T wave) predicted mortality (111 900±164 700 versus 85 600±144 800 between dead and alive patients, P <0.0002; and 0.43±0.62% versus 0.33±0.56%, P <0.0005 for the absolute and relative T-wave residuum, respectively). On Cox regression analysis entering age, left ventricular ejection fraction, echocardiographic left ventricular hypertrophy, and either of the T-wave residua, risk prediction was independent for the absolute (P =0.022) and for the relative (P =0.006) T-wave residuum, respectively, with age (P <0.0001), presence of left ventricular hypertrophy (P =0.002), and left ventricular ejection fraction (P =0.004) also being predictors of survival. Conclusions—The heterogeneity of myocardial repolarization, measured by the so-called T-wave residuum in the ECG, confers long-term independent prognostic information in US veterans with cardiovascular disease.