Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and Impact of Sleep Disordered Breathing in Patients with Severe Aortic Stenosis

Background Unlike the well-established association between sleep disordered breathing (SDB) and chronic heart failure, the relationship between SDB and severe aortic stenosis (AS) is not well investigated. Given the increasing prevalence of AS, and the improving prognosis of high risk AS patients attributable to transcatheter aortic valve implantation (TAVI), the prevalence and impact of SDB needs to be better understood. Methods and Results In this study, 140 patients with severe AS underwent polygraphy prior to TAVI. Clinical and hemodynamic parameters were recorded. Patients were followed for 573±405 days. We found that 99/140 patients (71%) had SDB with a mean apnoea-hypopnoea-index of 24±17/h. SDB was mild in 27%, moderate in 23% and severe in 21% of patients. In addition, 35 patients (25%) had obstructive sleep apnoea (OSA), whereas 64 patients (46%) had central sleep apnoea (CSA). Patients with OSA had predominantly mild SDB (20/38 pts.), and patients with CSA mostly had severe SDB (24/29 pts.). The prevalence and distribution of OSA and CSA were independent of left ventricular function. Overall, 1 and 2 year survival rates (74% and 71%, resp.) did not differ significantly between patients without SDB or those with OSA and CSA (p=0.81). Conclusions SDB, with a preponderance of CSA, was found to be highly prevalent in patients with high-grade AS scheduled for TAVI. SDB prevalence was independent of left ventricular function. Mortality after TAVI was not influenced by the type or severity of SDB.
Cellular Mechanisms of Neurovascular Damage and Repair After Stroke

The biological processes underlying stroke are complex, and patients have a narrow repertoire of therapeutic opportunities. After the National Institutes of Health (NIH) convened the Stroke Progress Review Group in 2001, stroke research shifted from having a purely neurocentric focus to adopting a more integrated view wherein dynamic interactions between all cell types contribute to function and dysfunction in the brain. This so-called “neurovascular unit” provides a conceptual framework that emphasizes cell–cell interactions between neuronal, glial, and vascular elements. Under normal conditions, signaling within the neurovascular unit helps maintain homeostasis. After stroke, cell–cell signaling is disturbed, leading to pathophysiology. More recently, emerging data now suggest that these cell–cell signaling mechanisms may also mediate parallel processes of neurovascular remodeling during stroke recovery. Because plasticity is a signature feature of the young and developing brain, these concepts may have special relevance to how the pediatric brain responds after stroke.
Building Connected Neighborhood Graphs for Locally Linear Embedding

Locally linear embedding is a nonlinear method for dimensionality reduction and manifold learning. It requires well-sampled input data in high dimensional space so that neighborhoods of all data points overlap with each other. In this paper, we build connected neighborhood graphs for the purpose of assigning neighbor points. A few methods are examined to build connected neighborhood graphs. They have made LLE applicable to a wide range of data including under-sampled data and non-uniformly distributed data. These methods are compared through experiments on both synthetic and real world data sets
Alcohol Consumption and Hiv Risk Behaviours: Integrating the Theories of Alcohol Myopia and Outcome-Expectancies

Reports have indicated that the use of alcohol is related to HIV risk related sexual behaviour (e.g. non-use of condoms during sexual intercourse). Studies suffer from methodological limitations such that causal conclusions about the role of alcohol in sexual risk taking are limited. Theories describing the association between alcohol and increased sexual risk behaviour have been suggested. Empirical findings may be limited and require re-examination within the theoretical context of the psychological processes that influence sexual decision-making. If processes are not explored and understood within theoretical boundaries, little advantage can be gained in the development of related interventions (e.g. health promotion) or significant clarification of the alcohol-sexual behaviour relationship. This paper discusses evidence from the alcohol expectancy literature and the alcohol myopia literature and emphasises the dynamic relationship between these sources. Relevant evidence is presented and integrated to provide a more comprehensive appreciation of possible psychological processes involved in sexual decision-making after the consumption of alcohol.
Involvement of TRAIL/TRAIL‐receptors in human intestinal cell differentiation

Despite the fact that tumor necrosis factor (TNF)‐related apoptosis inducing ligand (TRAIL) and its receptors (TRAIL‐Rs) are expressed in intestinal mucosa, little is known about the biological role of this system in intestinal cell physiology. The expression of surface TRAIL and TRAIL‐R1, ‐R2, ‐R3, ‐R4 were examined by flow cytometry in the immortalized human cell line tsFHI under culture conditions promoting growth or growth arrest and expression of differentiated traits. A progressive increase of surface TRAIL expression paralleled tsFHI differentiation, consistently with immunohistochemistry analysis showing an increase of TRAIL immunostaining along the crypt–villus axis in normal jejuneal mucosa. In spite of the presence of TRAIL‐R1 and TRAIL‐R2 “death receptors,” recombinant TRAIL was not cytotoxic for tsFHI cells. Exposure of tsFHI to recombinant TRAIL rather increased/anticipated the expression levels of the cyclin‐dependent kinase inhibitors p21 and p27, which mediate the induction of growth arrest and the stabilization of differentiated traits, respectively, as well as of the canonical differentiation marker DPPIV. The differentiation inducing activity of TRAIL was abolished by pre‐incubation with a Fc‐TRAIL‐R2 chimera. On the other hand, TRAIL did not significantly modulate the levels of osteoprotegerin (OPG), CXCL8/IL‐8, CXCL9/MIG, and CXCL10/IP10 spontaneously released or induced by inflammatory cytokines. Taken together, these data suggest that TRAIL might act as a paracrine trophic cytokine on intestinal epithelium, promoting intestinal cell differentiation. J.Cell. Physiol. © 2005 Wiley‐Liss, Inc.
Induction of Drug Metabolism: The Role of Nuclear Receptors

Induction of drug metabolism was described more than 40 years ago. Progress in understanding the molecular mechanism of induction of drug-metabolizing enzymes was made recently when the important roles of the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR), two members of the nuclear receptor superfamily of transcription factors, were discovered to act as sensors for lipophilic xenobiotics, including drugs. CAR and PXR bind as heterodimeric complexes with the retinoid X receptor to response elements in the regulatory regions of the induced genes. PXR is directly activated by xenobiotic ligands, whereas CAR is involved in a more complex and less well understood mechanism of signal transduction triggered by drugs. Most recently, analysis of these xenobiotic-sensing nuclear receptors and their nonmammalian precursors such as the chicken xenobiotic receptor suggests an important role of PXR and CAR also in endogenous pathways, such as cholesterol and bile acid biosynthesis and metabolism. In this review, recent findings regarding xenosensors and their target genes are summarized and are put into an evolutionary perspective in regard to how a living organism has derived a system that is able to deal with potentially toxic compounds it has not encountered before.
Comprehensive Assessment of Student Retention in Online Learning Environments

As the growth of online programs continues to rapidly accelerate, concern over the retention of the online learner is increasing. Educational administrators at institutions offering online courses, those fully online or brick and mortars, are eager to promote student achievement. Retention is critically important, not just for student success, but also for the success of these institutions of higher education. Models for understanding student persistence in the face-to-face environment are well established; however, many of the variables in these constructs are not present in the online environment or they manifest in significantly different ways. With attrition rates higher than in face-to-face programs, the development of models to explain online retention is considered imperative. This study moves in that direction by exploring the relationship between student demographics and interactions, and retention at a large online university. Analysis of data, which included an n of 20,569, provides an illustration of the importance of transfer credit and the consistency of activity in predicting continued enrollment.
Language Use in Eating Disorder Blogs

Social media have become a significant means for peer-related communication, self-presentation, and identity management. So-called eating disorder websites that propagate a drastic thin ideal and unhealthy eating behaviors have triggered a debate about the harmful facets of social Internet activity. Little research has addressed the language that is used by the authors of these websites. The present study focuses on personal weblogs, a popular form of mostly text-based, diary-like, online journals. We compared 31 pro–eating disorder blogs, 29 recovery blogs, and 27 control blogs by the means of computerized quantitative text analyses. The language of pro–eating disorder blogs featured lower cognitive processing, a more closed-minded writing style, was less emotionally expressive, contained fewer social references, and focused more on eating-related contents than recovery blogs. A subset of 12 language indicators correctly classified the blogs in 84% of the cases. The distinct language patterns appear to reflect the psychological conditions of the blog authors and provide insight into their various stages of coping.
A Page-based Hybrid (Software-Hardware) Dynamic Memory Allocator

Modern programming languages often include complex mechanisms for dynamic memory allocation and garbage collection. These features drive the need for more efficient implementation of memory management functions, both in terms of memory usage and execution performance. In this paper, we introduce a software and hardware co-design to improve the speed of the software allocator used in free-BSD systems. The hardware complexity of our design is independent of the dynamic memory size, thus making the allocator suitable for any memory size. Our design improves the performance of memory management intensive benchmarks by as much as 43%. To oar knowledge, this is the first-ever work of this kind, introducing "hybrid memory allocator"
Software Reliability Model with Optimal Selection of Failure Data

The possibility of obtaining more accurate predictions of future failures by excluding or giving lower weight to the earlier failure counts is suggested. Although data aging techniques such as moving average and exponential smoothing are frequently used in other fields, such as inventory control, the author did not find use of data aging in the various models surveyed. A model that includes the concept of selecting a subset of the failure data is the Schneidewind nonhomogeneous Poisson process (NHPP) software reliability model. In order to use the concept of data aging, there must be a criterion for determining the optimal value of the starting failure count interval. Four criteria for identifying the optimal starting interval for estimating model parameters are evaluated The first two criteria treat the failure count interval index as a parameter by substituting model functions for data vectors and optimizing on functions obtained from maximum likelihood estimation techniques. The third uses weighted least squares to maintain constant variance in the presence of the decreasing failure rate assumed by the model. The fourth criterion is the familiar mean square error. It is shown that significantly improved reliability predictions can be obtained by using a subset of the failure data. The US Space Shuttle on-board software is used as an example. >
v-Src SH3-enhanced Interaction with Focal Adhesion Kinase at β1 Integrin-containing Invadopodia Promotes Cell Invasion*

In viral Src (v-Src)-transformed cells, focal adhesion kinase (FAK) associates with v-Src by combined v-Src SH2 and gain-of-function v-Src SH3 domain binding to FAK. Here we assess the significance of the Arg-95 to Trp gain-of-function mutation in the v-Src SH3 domain through comparisons of Src−/− fibroblasts transformed with either Prague C v-Src or a point mutant (v-Src-RT) containing a normal (Arg-95) SH3 domain. Both v-Src isoforms exhibited equivalent kinase activity, enhanced Src−/− cell motility, and stimulated cell growth in both low serum and soft agar. The stability of a v-Src·FAK signaling complex and FAK phosphorylation at Tyr-861 and Tyr-925 were reduced in v-Src-RT- compared with v-Src-transformed cells. v-Src but not v-Src-RT promoted Src−/− cell invasion through a reconstituted Matrigel basement membrane barrier and v-Src co-localized with FAK and β1 integrin at invadopodia. In contrast, v-Src-RT exhibited a partial perinuclear and focal contact distribution in Src−/− cells. Adenovirus-mediated FAK overexpression promoted v-Src-RT recruitment to invadopodia, the formation of a v-Src-RT·FAK signaling complex, and reversed the v-Src-RT invasion deficit. Adenovirus-mediated inhibition of FAK blocked v-Src-stimulated cell invasion. These studies establish that gain-of-function v-Src SH3 targeting interactions with FAK at β1 integrin-containing invadopodia act to stabilize a v-Src·FAK signaling complex promoting cell invasion.
Purification and identification of a transcription factor, USF‐2, binding to E‐box element in the promoter of human telomerase reverse transcriptase (hTERT)

Controversy remains about the identity of the transcription factor(s) (TFs), which bind to the two E‐box elements (CACGTG, proximal and distal) of the human telomerase (hTERT) gene promoter, the essential elements in the regulation of telomerase. Here, systematic oligonucleotide trapping supplemented with 2‐DE and proteomic methods was used to identify E‐box binding TFs. Although insufficient purity was obtained from the proximal E‐box element trapping, further fractionation provided by 2‐DE and specific identification from Southwestern blotting analysis allow us to clearly identify an E‐box binding TF. The protein spot was cut from 2‐DE and in‐gel digested with trypsin for LC‐nanospray ESI‐MS/MS analysis. This identified upstream stimulatory factor 2 (USF2). Western blotting analysis with specific antibodies clearly shows USF2 present in the purified fraction and USF2 antibody supershifts the specific DNA‐binding complex on non‐denaturing gels. Furthermore, a novel method was developed in which the specific DNA‐TF complex was separated on a non‐denaturing gel, the band was cut and applied to SDS‐PAGE for a second dimension. Western blots of this second gel also confirmed the presence of USF2.
MASS RESPONSIVENESS IN THE CENTRAL NERVOUS SYSTEM

A review of the literature relevant to the present study discloses certain controversial matters on which our report may throw additional light, notably the concepts of "cerebral localization," inherent rhythm of afferent and on-relaying mechanisms and the genesis of action currents from muscles. The interpretation of the doctrine of cerebral localization of function is changing from a rigid to a more liberal one. The results of present-day work in neurophysiology are steadily attesting to the advisability of such a modification. 1 Past workers have invested sensory and central neural mechanisms with inherent specificities of response implying only the final motor pathway to be capable of aperiodic rhythm. Here we are unable to find any characteristic rhythm that is not common to every part of the conducting stimulus-response circuit. 2 To date, the origin of the electromyographically determined action current frequencies is in question. Whether it is resident in the central
Professionals: Back to the Future?

This article examines empirical evidence on the impact of the introduction of a quasi-market in healthcare in the UK on professionals, especially doctors. Data are drawn from two longitudinal studies occurring between 1990 and 1994, of aspects of the changes to the health system. Data collection involved a range of methods, including observation, interviews, questionnaires and archival material. The findings show that a unilateral analysis of the impact of the quasimarket on professionals is inadequate to understand the situation. The responses of the professionals to change have had a major influence on the outcomes. Professionals have not uniformly lost power, some have gained considerably. Explanations of the variance of impact and the substantial power shifts have to take account of a range of contextual factors. The market has not had a major impact on the technical autonomy of the doctors. Consequential structural changes have produced a new category of professional managers who are actively managing their colleagues' performance.
Diabetic neuropathies: a statement by the American Diabetes Association.

The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. This statement is based on two recent technical reviews (1,2), to which the reader is referred for detailed discussion and relevant references to the literature. An internationally agreed simple definition of DPN for clinical practice is “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (3). However, the diagnosis cannot be made without a careful clinical examination of the lower limbs, as absence of symptoms should never be assumed to indicate an absence of signs. This definition conveys the important message that not all patients with peripheral nerve dysfunction have a neuropathy caused by diabetes. Confirmation can be established with …
Nanostructured lipid carriers and their current application in targeted drug delivery

In the last few decades, various drug-delivery technologies have emerged and a fascinating part of this has been the development of nanoscale drug delivery devices. Nanoparticles (NPs) and other colloidal drug-delivery systems modify the kinetics, drug distribution in the body and release profile of an associated drug. Nanostructured lipid carriers (NLCs) have been reported to be an alternative system to emulsions, liposomes, microparticles, solid lipid nanoparticles (SLNs) and their polymeric counterparts due to their numerous advantages. This paper basically reviews the types of NLCs, mechanism of skin penetration, stability related issues along with their production techniques, characterisation and applications towards targeted drug delivery.
Red Ginseng Extract Attenuates Kainate-Induced Excitotoxicity by Antioxidative Effects

This study investigated the neuroprotective activity of red ginseng extract (RGE, Panax ginseng, C. A. Meyer) against kainic acid- (KA-) induced excitotoxicity in vitro and in vivo. In hippocampal cells, RGE inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the MTT assay. To study the possible mechanisms of the RGE-mediated neuroprotective effect against KA-induced cytotoxicity, we examined the levels of intracellular reactive oxygen species (ROS) and [Ca2+]i in cultured hippocampal neurons and found that RGE treatment dose-dependently inhibited intracellular ROS and [Ca2+]i elevation. Oral administration of RGE (30 and 200 mg/kg) in mice decreased the malondialdehyde (MDA) level induced by KA injection (30 mg/kg, i.p.). In addition, similar results were obtained after pretreatment with the radical scavengers Trolox and N, N′-dimethylthiourea (DMTU). Finally, after confirming the protective effect of RGE on hippocampal brain-derived neurotropic factor (BDNF) protein levels, we found that RGE is active compounds mixture in KA-induced hippocampal mossy-fiber function improvement. Furthermore, RGE eliminated 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the IC50 was approximately 10 mg/ml. The reductive activity of RGE, as measured by reaction with hydroxyl radical (•OH), was similar to trolox. The second-order rate constant of RGE for •OH was 3.5–4.5 × 109 M−1·S−1. Therefore, these results indicate that RGE possesses radical reduction activity and alleviates KA-induced excitotoxicity by quenching ROS in hippocampal neurons.