Miracle-dz/UniFAR-FTUs huggingface dataset:
Stable occurrence of knee and hip total joint replacement in Central Finland between 1986 and 2003: an indication of improved long-term outcomes of rheumatoid arthritis

Background: Total joint replacement (TJR) surgery is an important severe long-term outcome of rheumatoid arthritis, but relatively little is known about changes of its incidence in patients with rheumatoid arthritis over the past two decades. Methods: A population-based, retrospective, incidence case review was conducted to analyse the frequency of primary TJR surgery of the knee and hip in all patients, and specifically in patients with rheumatoid arthritis in Central Finland between 1986 and 2003. Patients with TJR surgery of the knee and hip were identified in hospital databases over the 18-year period. Age-standardised incidence rate ratios for the primary TJR of the knee and hip were calculated, stratified to sex and diagnosis, with 1986 as the reference value. Results: In patients without rheumatoid arthritis the age-adjusted incidence rate ratios (with 95% CI) for TJR of the knee increased 9.8-fold from 1986 to 2003 in women and men, and for TJR of the hip 1.8-fold in women and 2-fold in men. By contrast, no meaningful change was seen over this period, in age-adjusted incidence rate ratios for TJR of the knee or hip in patients with rheumatoid arthritis, ranging from 0.7 to 1.2 in 2003 compared with 1986. Conclusion: The prevalence of TJR surgery has increased 2–10-fold in patients without rheumatoid arthritis patients, associated with an ageing population, but has not increased in patients with rheumatoid arthritis between 1986 and 2003. These data are consistent with emerging evidence that long-term outcomes of rheumatoid arthritis have improved substantially, even before the availability of biological agents.
Endogenous signalling pathways and caged IP3 evoke Ca2+ puffs at the same abundant immobile intracellular sites

ABSTRACT The building blocks of intracellular Ca2+ signals evoked by inositol 1,4,5-trisphosphate receptors (IP3Rs) are Ca2+ puffs, transient focal increases in Ca2+ concentration that reflect the opening of small clusters of IP3Rs. We use total internal reflection fluorescence microscopy and automated analyses to detect Ca2+ puffs evoked by photolysis of caged IP3 or activation of endogenous muscarinic receptors with carbachol in human embryonic kidney 293 cells. Ca2+ puffs evoked by carbachol initiated at an estimated 65±7 sites/cell, and the sites remained immobile for many minutes. Photolysis of caged IP3 evoked Ca2+ puffs at a similar number of sites (100±35). Increasing the carbachol concentration increased the frequency of Ca2+ puffs without unmasking additional Ca2+ release sites. By measuring responses to sequential stimulation with carbachol or photolysed caged IP3, we established that the two stimuli evoked Ca2+ puffs at the same sites. We conclude that IP3-evoked Ca2+ puffs initiate at numerous immobile sites and the sites become more likely to fire as the IP3 concentration increases; there is no evidence that endogenous signalling pathways selectively deliver IP3 to specific sites. Summary: Ca2+ puffs are the building blocks for IP3-evoked Ca2+ signals. Ca2+ puffs evoked by caged IP3 or via endogenous signalling pathways initiate at the same fixed intracellular sites.
The Latent Structure of Dictionaries

How many words-and which ones-are sufficient to define all other words? When dictionaries are analyzed as directed graphs with links from defining words to defined words, they reveal a latent structure. Recursively removing all words that are reachable by definition but that do not define any further words reduces the dictionary to a Kernel of about 10% of its size. This is still not the smallest number of words that can define all the rest. About 75% of the Kernel turns out to be its Core, a "Strongly Connected Subset" of words with a definitional path to and from any pair of its words and no word's definition depending on a word outside the set. But the Core cannot define all the rest of the dictionary. The 25% of the Kernel surrounding the Core consists of small strongly connected subsets of words: the Satellites. The size of the smallest set of words that can define all the rest-the graph's "minimum feedback vertex set" or MinSet-is about 1% of the dictionary, about 15% of the Kernel, and part-Core/part-Satellite. But every dictionary has a huge number of MinSets. The Core words are learned earlier, more frequent, and less concrete than the Satellites, which are in turn learned earlier, more frequent, but more concrete than the rest of the Dictionary. In principle, only one MinSet's words would need to be grounded through the sensorimotor capacity to recognize and categorize their referents. In a dual-code sensorimotor/symbolic model of the mental lexicon, the symbolic code could do all the rest through recombinatory definition.
Living with urinary incontinence: a longitudinal study of older women.

BACKGROUND urinary incontinence carries major social burden and considerable costs for health care systems. OBJECTIVE the aim of this study was to investigate changes in continence status among a large cohort of older women, and to identify factors associated with incidence of incontinence in later life. SUBJECTS participants of the Australian Longitudinal Study of Women's Health (ALSWH), aged 70-75 years in 1996 and who have completed four health surveys over the past 10 years. METHODS continence status across four survey periods, spanning 9 years, were defined according to women's reports of 'leaking urine' at each survey. Generalised estimating equation (GEE) models were used in longitudinal analyses of the factors associated with changing continence status over time. RESULTS this study presents longitudinal data on the prevalence and incidence of incontinence from a large cohort of older women, over 9 years of follow-up. Over this time, 14.6% (95% CI 13.9-15.3) of the women in the study who had previously reported leaking urine 'rarely' or 'never' developed incontinence, and 27.2% (95% CI 26.2%, 28.3%) of women participating in Survey 4 (S4) in 2005 reported leaking urine 'sometimes' or 'often' at that survey, with women being twice as likely to report incontinence at S4 as they were 6 years earlier. Longitudinal models demonstrated the association between incontinence and dementia (P < 0.001; OR = 2.34; 95% CI 1.64, 3.34), dissatisfaction with physical ability (P < 0.001; OR = 1.70; 95% CI 1.52, 1.89), falls to the ground (P <0.001; OR = 1.23; 95% CI 1.13, 1.33), BMI (P < 0.001; OR = 2.18; 95% CI 1.70, 2.80 for obese), constipation (P < 0.001; OR 1.46; 95% CI 1.34-1.58), urinary tract infection (P < 0.001; OR 2.07; 95% CI 1.89-2.28), history of prolapse (P </= 0.001; OR = 1.53; 95% CI 1.35, 1.74) and prolapse repair (P = 0.002; OR = 1.23; 95% CI 1.08, 1.40). Stroke (P = 0.01), parity (P = 0.017) and hysterectomy (P = 0.026) and number of visits to the general practitioner (P = 0.040) were less strongly associated with incontinence in the final longitudinal model. Incontinence was not significantly associated with area of residence (P = 0.344), education (P = 0.768), smoking (P = 0.055), diabetes (P = 0.072), attending support groups (P = 0.464) or attending social groups (P = 0.022). CONCLUSION strong associations between BMI, dysuria and constipation indicate key opportunities to prevent incontinence among older women.
A Spiking Neural Integrator Model of the Adaptive Control of Action by the Medial Prefrontal Cortex

Subjects performing simple reaction-time tasks can improve reaction times by learning the expected timing of action-imperative stimuli and preparing movements in advance. Success or failure on the previous trial is often an important factor for determining whether a subject will attempt to time the stimulus or wait for it to occur before initiating action. The medial prefrontal cortex (mPFC) has been implicated in enabling the top-down control of action depending on the outcome of the previous trial. Analysis of spike activity from the rat mPFC suggests that neural integration is a key mechanism for adaptive control in precisely timed tasks. We show through simulation that a spiking neural network consisting of coupled neural integrators captures the neural dynamics of the experimentally recorded mPFC. Errors lead to deviations in the normal dynamics of the system, a process that could enable learning from past mistakes. We expand on this coupled integrator network to construct a spiking neural network that performs a reaction-time task by following either a cue-response or timing strategy, and show that it performs the task with similar reaction times as experimental subjects while maintaining the same spiking dynamics as the experimentally recorded mPFC.
Visual Psychophysics and Physiological Optics Dark-Adaptation Functions in Molecularly Confirmed Achromatopsia and the Implications for Assessment in Retinal Therapy Trials

Citation: Aboshiha J, Luong V, Cowing J, et al. Dark-adaptation functions in molecularly confirmed achromatopsia and the implications for assessment in retinal therapy trials. Invest Ophthalmol Vis Sci. 2014;55:6340–6349. DOI:10.1167/iovs.14-14910 PURPOSE. To describe the dark-adaptation (DA) functions in subjects with molecularly proven achromatopsia (ACHM) using refined testing conditions with a view to guiding assessment in forthcoming gene therapy trials.
Effect of intranasal reovirus infection on antibacterial activity of mouse lung.

The lung in the normal mouse is capable of disposing of large numbers of inhaled viable bacteria [1, 2]. The process is highly efficient and appears to be due, in large part, to an intrapulmonary bactericidal mechanism [3]. Influenza viral infection of mice was shown to impair this mechanism [4-10], but information on the effect of other viruses is scant in spite of recent advances in our understanding of many agents that cause respiratory infections in animals and man. The present studies were designed to elucidate the effects of intranasal (i.n.) infection with reovirus on the elimination of viable bacteria from the lungs of mice after such infection. Inoculation of reovirus i.n. causes
SR Proteins: Binders, Regulators, and Connectors of RNA

Serine and arginine-rich (SR) proteins are RNA-binding proteins (RBPs) known as constitutive and alternative splicing regulators. As splicing is linked to transcriptional and post-transcriptional steps, SR proteins are implicated in the regulation of multiple aspects of the gene expression program. Recent global analyses of SR-RNA interaction maps have advanced our understanding of SR-regulated gene expression. Diverse SR proteins play partially overlapping but distinct roles in transcription-coupled splicing and mRNA processing in the nucleus. In addition, shuttling SR proteins act as adaptors for mRNA export and as regulators for translation in the cytoplasm. This mini-review will summarize the roles of SR proteins as RNA binders, regulators, and connectors from transcription in the nucleus to translation in the cytoplasm.
Geometry of homoclinic Connections in a Planar Circular Restricted Three-Body Problem

The stable and unstable invariant manifolds associated with Lyapunov orbits about the libration point L1 between the primaries in the planar circular restricted three-body problem with equal masses are considered. The behavior of the intersections of these invariant manifolds for values of the energy between that of L1 and the other collinear libration points L2, L3 is studied using symbolic dynamics. Homoclinic orbits are classified according to the number of turns about the primaries.
Beneficial Effects of Extended Growth Hormone Treatment After Hospital Discharge in Pediatric Burn Patients

Objective:To study the efficacy of growth hormone given to severely burned children from discharge to 12 months after burn and for 12 months after the drug was discontinued. Summary Background Data:We have previously shown that low-dose recombinant human growth hormone (rhGH), given to children after a severe thermal injury, successfully improved lean muscle mass, bone mineral content, and growth. The aim of the present study was to investigate long-term functional improvements after treatment. Methods:Forty-four pediatric patients with over 40% total body surface area burns were studied for 24 months after burn. Patients were randomized to receive either rhGH (0.05 mg/kg body weight) or placebo. Height, weight, body composition, serum hormones, resting energy expenditure, cardiac function, muscle strength, and number of reconstructive procedures performed were measured during rhGH treatment and for 12 months after treatment was discontinued. Statistical analysis used Tukey's multiple comparison test. Significance was accepted at P < 0.05. Results:Height, weight, lean body mass, bone mineral content, cardiac function, and muscle strength significantly improved during rhGH treatment compared with placebo (P < 0.05). This treatment significantly increased GH, IGF-I, and IGFBP-3, whereas serum cortisol decreased (P < 0.05). The number of operative reconstructive procedures was significantly lower with rhGH (P < 0.05). Improvements in height, bone mineral content, and IGF-1 concentrations persisted after rhGH treatment (P < 0.05). No side effects with rhGH were observed. Conclusions:Administration of rhGH for 1 year after burn was safe and improved recovery. These salutary effects continued after rhGH treatment was discontinued.
Dual-Polarization C-Band Radar Observations of Sea Ice in the Amundsen Gulf

Polarimetric observations of sea ice from synthetic aperture radar can, in principle, assist in sea-ice classification and ice-water discrimination. In this paper, we use dual-polarization ground-based scatterometer observations of sea ice to assess the potential value of spaceborne dual-polarization observations of sea ice for operational ice analysis, focusing on C-band and, in particular, the contribution of the HV backscatter coefficient and HH/VV polarization ratios. Results show that signature variability resulting from frost flowers, ice deformation, and snow cover can overwhelm systematic differences between younger ice types, up to first-year thin. As a result of this and noise floor limitations of spaceborne sensors, the HV backscatter coefficient makes visual ice type and open water discrimination easier only below about 30° incidence angle. The HH/VV ratio is less impacted by the noise floor of spaceborne sensors but retains similar ambiguities for sea-ice classification.
Learning about Environmental Geometry: an Associative Model

K. Cheng (1986) suggested that learning the geometry of enclosing surfaces takes place in a geometric module blind to other spatial information. Failures to find blocking or overshadowing of geometry learning by features near a goal seem consistent with this view. The authors present an operant model in which learning spatial features competes with geometry learning, as in the Rescorla–Wagner model. Relative total associative strength of cues at a location determines choice of that location and thus the frequencies of reward paired with each cue. The model shows how competitive learning of local features and geometry can appear to result in potentiation, blocking, or independence, depending on enclosure shape and kind of features. The model reproduces numerous findings from dry arenas and water mazes. Cheng (1986) was the first to show that animals can use the geometry of an enclosure to locate a hidden goal. In a working memory task, he found that distinctive corner panels did not prevent rats from learning about the shape of a rectangular enclosure and that rats sometimes ignored the panels and searched for a hidden reward at the diagonally opposite, geometrically identical, corner of the enclosure, dubbed the rotational corner (see Figure 1). Cheng concluded that shape parameters of the enclosure are learned separately from featural information in a specialized geometric module. Later studies have shown that, in a reference memory version of Cheng's task, features are also eventually geometry in a similar way (see review in Cheng & Newcombe, 2005). Studies of geometry learning raise two essentially separate issues. One is, what is encoded in geometry learning? This debate has centered on whether animals extract some global parameter of a space, such as its principal axis, or use local geometric features, such as sizes of angles and sides (see Cheng & Gallistel, 2005). Here we focus on the other fundamental issue in the area: How does learning based on the hypothesized geometric module interact with learning based on other spatial cues? In the most recent version of the geometric module hypothesis, Cheng and New-combe (2005; see also Cheng, 2005b) suggested several interpretations for the modularity of geometric information. Rather than being entirely separate from processing of features, geometry could combine with featural information in memory or in determining performance. (2001) were apparently the first to point out that reliance on geometric cues for learning the location of a goal, even in the presence …
The Influence of Implicit Hand-Based Representations on Mental Arithmetic

Recently, a strong functional relationship between finger counting and number processing has been suggested. It has been argued that bodily experiences such as finger counting may influence the structure of the basic mental representations of numbers even in adults. However, to date it remains unclear whether the structure of finger counting systems also influences educated adults’ performance in mental arithmetic. In the present study, we pursued this question by examining finger-based sub-base-five effects in an addition production task. With the standard effect of a carry operation (i.e., base-10 crossing) being replicated, we observed an additional sub-base-five effect such that crossing a sub-base-five boundary led to a relative response time increase. For the case of mental arithmetic sub-base-five effects have previously been reported only in children. However, it remains unclear whether finger-based numerical effects in mental arithmetic reflect an important but transitory step in the development of arithmetical skills. The current findings suggest that even in adults embodied representations such as finger counting patterns modulate arithmetic performance. Thus, they support the general idea that even seemingly abstract cognition in adults may at least partly be rooted in our bodily experiences.
Reliability of four experimental mechanical pain tests in children

Purpose In order to study pain in children, it is necessary to determine whether pain measurement tools used in adults are reliable measurements in children. The aim of this study was to explore the intrasession reliability of pressure pain thresholds (PPT) in healthy children. Furthermore, the aim was also to study the intersession reliability of the following four tests: (1) Total Tenderness Score; (2) PPT; (3) Visual Analog Scale score at suprapressure pain threshold; and (4) area under the curve (stimulus–response functions for pressure versus pain). Participants and methods Twenty-five healthy school children, 8–14 years of age, participated. Test 2, PPT, was repeated three times at 2 minute intervals on the same day to estimate PPT intrasession reliability using Cronbach’s alpha. Tests 1–4 were repeated after median 21 (interquartile range 10.5–22) days, and Pearson’s correlation coefficient was used to describe the intersession reliability. Results The PPT test was precise and reliable (Cronbach’s alpha ≥ 0.92). All tests showed a good to excellent correlation between days (intersessions r = 0.66–0.81). There were no indications of significant systematic differences found in any of the four tests between days. Conclusion All tests seemed to be reliable measurements in pain evaluation in healthy children aged 8–14 years. Given the small sample size, this conclusion needs to be confirmed in future studies.
Glomerular filtration rate is a confounder for the measurement of soluble mesothelin in serum.

The mesothelin gene encodes a 71-kDa precursor protein that is subsequently cleaved into a soluble megakaryocyte potentiating factor and a membrane-bound part, mesothelin. Mesothelin can be shed as “soluble mesothelin” or “soluble mesothelin-related protein” (SMRP),1 which is an approximately 40-kDa biomarker of malignant mesothelioma, an asbestos-related cancer (1). Mesothelioma typically occurs in middle-aged men, and the renal function or the glomerular filtration rate (GFR) can occasionally decrease in these patients and in individuals at risk of developing mesothelioma. Renal impairment leads to the accumulation of low molecular weight proteins in the blood [e.g., cystatin C (13 kDa) and β-trace protein (BTP) (23–29 kDa)], and these proteins have been used as markers of the GFR. Such renal impairment can also cause the accumulation of soluble mesothelin, as has previously been reported for a limited number of cases(2). Our aim, therefore, was to thoroughly investigate the impact of renal function on serum SMRP concentrations. We enrolled 66 individuals (49 men and 17 women; median age, 58 years; range, 24–80 years), who were referred for measurement of 51Cr-EDTA clearance to estimate the GFR. We excluded patients with asbestos-related diseases/malignancies, patients with endometrial, ovarian, cervix, lung, breast, pancreatic, or gastrointestinal cancer, and patients with leukemia, because these conditions can overexpress mesothelin (3)(4). The study was approved by the ethics committee of both participating hospitals, and participants gave written informed consent. …
Flow-Based Network Analysis of the Caenorhabditis elegans Connectome

We exploit flow propagation on the directed neuronal network of the nematode C. elegans to reveal dynamically relevant features of its connectome. We find flow-based groupings of neurons at different levels of granularity, which we relate to functional and anatomical constituents of its nervous system. A systematic in silico evaluation of the full set of single and double neuron ablations is used to identify deletions that induce the most severe disruptions of the multi-resolution flow structure. Such ablations are linked to functionally relevant neurons, and suggest potential candidates for further in vivo investigation. In addition, we use the directional patterns of incoming and outgoing network flows at all scales to identify flow profiles for the neurons in the connectome, without pre-imposing a priori categories. The four flow roles identified are linked to signal propagation motivated by biological input-response scenarios.