Miracle-dz/UniFAR-FTUs huggingface dataset:
Living with chronic obstructive pulmonary disease: The stories of frequent attenders to the Emergency Department

AIMS AND OBJECTIVES To explore the experiences of chronic obstructive pulmonary disease (COPD) amongst individuals who have a high frequency of presentations to the Emergency Department and their carers. BACKGROUND Patients with COPD are amongst the most frequent attenders in the Emergency Department despite the chronic nature of their condition. Good self-management has previously been identified as a key to maintaining health and reducing COPD exacerbations. There has been limited investigation of those with COPD who frequently attend the Emergency Department. DESIGN Descriptive qualitative phase of a mixed methods study. METHODS Individuals who had attended an Emergency Department within a single health district at least three times in the previous year for COPD were invited to participate in semistructured face-to-face interviews. A total of 19 individuals consented to participate, of whom 12 were male. Half of the interviews included both those with COPD and carers. Data were audio-recorded and transcribed, before being analysed using thematic analysis. RESULTS Five main themes emerged from the data, namely (i) a sense of grief, loss and guilt, yet hope for the future; (ii) the impact on carers; (iii) the end point of self-management; (iv) the healthcare experience; and (v) the primary care experience. CONCLUSION The experience of individuals with COPD who frequently present to the Emergency Department and their carers highlights the complexity of living with this disease. Providing effective intervention to manage exacerbation requires an understanding of the issues that are faced by patients and their carers. Clear systems and skills for sharing information are essential to decrease avoidable use of the Emergency Department.
The Cost and Efficacy of Home Care for Patients With Chronic Lung Disease

A randomized controlled trial was conducted to assess efficacy and cost of sustained home nursing care for patients with chronic lung disease. Three hundred one patients were randomly assigned to a respiratory home care group (RHC) that received care from respiratory home care nurses, a standard home care group (SHC) that received care from regular home care nurses, or an office care group (OC) that received whatever care they needed except for home care. Patients were followed for 1 year. At the end of the study year, there was no difference in survival, pulmonary function, or everyday functioning among the three groups. Average annual cost of care for all study patients was $7,647 (1981–82 dollars). The average annual health care costs for patients in the RHC group was $9,768; for those in the SHC group, $8,058; and for those in the OC group, $5,051 (P = 6.45, df = 2/298, P = 0.02). These results suggest that the current policy of limited coverage of home nursing services by Medicare and other third-party payers may be appropriate.
Brain Access and Anticonvulsant Efficacy of Carbamazepine, Lamotrigine, and Felbamate in ABCC2/MRP2‐Deficient TR− Rats

Summary: Purpose: Different adenosine triphosphate (ATP)‐driven multidrug transporters have been described to be expressed in the luminal membrane of blood–brain barrier (BBB) endothelial cells. At this site, multidrug transporters have been suggested to restrict penetration of drugs into the brain. Increasing evidence suggests that overexpression of different multidrug transporters occurs in the region of the epileptic focus of pharmacoresistant epilepsy patients. Based on the assumption that antiepileptic drugs (AEDs) are substrates of these transporters, this overexpression may limit access of AEDs to epileptic neurons and may contribute to drug‐refractoriness. In a recent study, overexpression of multidrug resistance protein 2 (ABCC2; MRP2) was reported in BBB endothelial cells of epileptic focal tissue from pharmacoresistant patients. With brain microdialysis, we recently demonstrated that the AED phenytoin is subject to transport by ABCC2 at the BBB, whereas phenobarbital does not seem to be a substrate of ABCC2.
Upper body training and the triceps brachii muscle of elite cross country skiers

This study aimed at evaluating whether addition of extensive upper body training in well‐trained cross country skiers induces an adaptation of the triceps brachii (TB) muscle and whether this affects performance. Muscle biopsies were obtained from TB muscle in six male elite cross country skiers before and after 20 weeks of increased upper body training. The cross‐sectional area of type I and IIA fibers increased by 11.3% and 24.0%, respectively, and so did the number of capillaries per fiber (2.3–3.2) (all P<0.05). SDS‐polyacrylamide electrophoresis revealed in single fibers that the number of fibers expressing myosin heavy chain (MHC) type I isoform decreased from 68.7% to 60.9% (P<0.05), MHC I/IIA isoform was unaltered, while MHC IIA fibers increased from 21.6% to 35.7% and the 4.8% MHC IIA/IIX disappeared with the training (both P<0.05). Citrate synthase and 3‐hydroxyacyl coenzyme A dehydrogenase activities increased by 23.3% and 15.4%, respectively, and double poling 10 km time‐trial by 10.4% (all P<0.05). The values for TB are similar to what has been demonstrated for leg muscles after exercise training. The subjects who demonstrated the largest improvement in performance exhibited the largest muscle adaptation, which, in turn, was related to the pre‐maximal oxygen uptake.
Dynamic modelling of n-of-1 data: powerful and flexible data analytics applied to individualised studies

ABSTRACT N-of-1 studies are based on repeated observations within an individual or unit over time and are acknowledged as an important research method for generating scientific evidence about the health or behaviour of an individual. Statistical analyses of n-of-1 data require accurate modelling of the outcome while accounting for its distribution, time-related trend and error structures (e.g., autocorrelation) as well as reporting readily usable contextualised effect sizes for decision-making. A number of statistical approaches have been documented but no consensus exists on which method is most appropriate for which type of n-of-1 design. We discuss the statistical considerations for analysing n-of-1 studies and briefly review some currently used methodologies. We describe dynamic regression modelling as a flexible and powerful approach, adaptable to different types of outcomes and capable of dealing with the different challenges inherent to n-of-1 statistical modelling. Dynamic modelling borrows ideas from longitudinal and event history methodologies which explicitly incorporate the role of time and the influence of past on future. We also present an illustrative example of the use of dynamic regression on monitoring physical activity during the retirement transition. Dynamic modelling has the potential to expand researchers’ access to robust and user-friendly statistical methods for individualised studies.
Stable RNA interference: comparison of U6 and H1 promoters in endothelial cells and in mouse brain

RNA interference (RNAi) is a post‐transcriptional RNA degradation process, which has become a very useful tool in gene function studies and gene therapy applications. Long‐term cellular expression of small interfering RNA (siRNA) molecules required for many gene therapy applications can be achieved by lentiviral vectors (LVs). The two most commonly used promoters to drive the short hairpin RNA (shRNA) expression are the human U6 small nuclear promoter (U6) and the human H1 promoter (H1).
μFEA successfully exhibits higher stresses and strains in microdamaged regions of whole vertebrae

Micro‐finite element (μFE) modeling has shown promise in evaluating the structural integrity of trabecular bone. Histologic microcrack analyses have been compared to μFE models of trabecular bone cores to demonstrate the potential of this technique. To date this has not been achieved in whole bone structures, and comparisons of histologic microcrack and μFE results have been limited due to challenges in alignment of 2D sections with 3D data sets. The goal of this study was to ascertain if image registration can facilitate determination of a relationship between stresses and strains generated from μFE models of whole vertebrae and histologically identified microdamage. μFE models of three whole vertebrae, stained sequentially with calcein and fuchsin, were generated with accurate integration of element sets representing the histologic sections based on volumetric image registration. Displacement boundary conditions were applied to the μFE models based on registration of loaded and unloaded μCT images. Histologically labeled damaged regions were found to have significantly higher von Mises stresses and principle strains in the μFE models, as compared to undamaged regions. This work provides a new robust method for generating and histologically validating μFE models of whole bones that can represent trabecular damage resulting from complex physiologic loading. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1653–1660, 2013
Markov chain evaluation of acute postoperative pain transition states

Abstract Previous investigations on acute postoperative pain dynamicity have focused on daily pain assessments, and so were unable to examine intraday variations in acute pain intensity. We analyzed 476,108 postoperative acute pain intensity ratings, which were clinically documented on postoperative days 1 to 7 from 8346 surgical patients using Markov chain modeling to describe how patients are likely to transition from one pain state to another in a probabilistic fashion. The Markov chain was found to be irreducible and positive recurrent, with no absorbing states. Transition probabilities ranged from 0.0031, for the transition from state 10 to state 1, to 0.69 for the transition from state 0 to state 0. The greatest density of transitions was noted in the diagonal region of the transition matrix, suggesting that patients were generally most likely to transition to the same pain state as their current state. There were also slightly increased probability densities in transitioning to a state of asleep or 0 from the current state. An examination of the number of steps required to traverse from a particular first pain score to a target state suggested that overall, fewer steps were required to reach a state of 0 (range 6.1-8.8 steps) or asleep (range 9.1-11) than were required to reach a mild pain intensity state. Our results suggest that using Markov chains is a feasible method for describing probabilistic postoperative pain trajectories, pointing toward the possibility of using Markov decision processes to model sequential interactions between pain intensity ratings, and postoperative analgesic interventions.
Reconfigurable Inductorless Wideband CMOS LNA for Wireless Communications

Future hyper-connected devices must support several communication standards, across various frequency bands, with a low-area, single-chip, radio frequency frontend. In this paper, we present a reconfigurable, inductorless, wideband, low-noise amplifier (LNA) for multistandard applications. This LNA is based on a complementary current-reuse common source amplifier, combined with a low-current active feedback. A gyrator-C effect is used to achieve wideband input matching. High linearity is obtained through complementary derivative superposition and active shunt feedback. Implemented in 130-nm CMOS technology, the prototype exhibits a -3 dB bandwidth of 2.2 GHz. In high linearity mode, the LNA achieves a minimum <inline-formula> <tex-math notation="LaTeX">$NF$ </tex-math></inline-formula> of 2 dB, a voltage gain of 21.1 dB and an <inline-formula> <tex-math notation="LaTeX">$IIP_{3}$ </tex-math></inline-formula> of +14.3 dBm, with 7 mW of power consumption. In low-power mode, it draws 1.5 mW, while providing a NF of 2.6 dB, a gain of 21 dB, and an <inline-formula> <tex-math notation="LaTeX">$IIP_{\mathrm {3}}$ </tex-math></inline-formula> of 4.7 dBm. The active die area is 0.0072 mm<sup>2</sup>.
The Extracellular Adenosine Deaminase Growth Factor, ADGF/CECR1, Plays a Role in Xenopus Embryogenesis via the Adenosine/P1 Receptor*

Adenosine deaminase-related growth factors (ADGF), also known as CECR1 in vertebrates, are a novel family of growth factors with sequence similarity to classical cellular adenosine deaminase. Although genes for ADGF/CECR1 have been identified in both invertebrates as well as vertebrates, their in vivo functions in vertebrates remain unknown. We isolated cDNA clones for two cerc 1s from Xenopus laevis. Both recombinant Xenopus CECR1s exhibited adenosine deaminase and growth factor activity, and the adenosine deaminase activity was found to be indispensable for growth factor activity. The Xenopus cerc 1s are expressed in the somites, pronephros, eyes, cement gland, neural tube, and neural floor plate of the embryos. Knock-down of these two genes using morpholino oligonucleotides caused a reduction in the body size and abnormalities of the body axis in the Xenopus embryos, accompanied by selective changes in the expression of developmental marker genes. Injection of adenosine, agonists for adenosine/P1 receptors, or adenosine deaminase inhibitor into late gastrula archenteron embryos resulted in developmental defects similar to those caused by morpholino oligonucleotide injection. These results show, for the first time, the involvement of CECR1s via the adenosine/P1 receptors in vertebrate embryogenesis via regulation of extracellular adenosine concentrations.
Reducing Binary Quadratic Forms for More Scalable Quantum Annealing

Recent advances in the development of commercial quantum annealers such as the D-Wave 2X allow solving NP-hard optimization problems that can be expressed as quadratic unconstrained binary programs. However, the relatively small number of available qubits (around 1000 for the D-Wave 2X quantum annealer) poses a severe limitation to the range of problems that can be solved. This paper explores the suitability of preprocessing methods for reducing the sizes of the input programs and thereby the number of qubits required for their solution on quantum computers. Such methods allow us to determine the value of certain variables that hold in either any optimal solution (called strong persistencies) or in at least one optimal solution (weak persistencies). We investigate preprocessing methods for two important NP-hard graph problems, the computation of a maximum clique and a maximum cut in a graph. We show that the identification of strong and weak persistencies for those two optimization problems is very instance-specific,but can lead to substantial reductions in the number of variables.
Chromosome walking shows a highly homologous repetitive sequence present in all the centromere regions of fission yeast

By cloning centromere‐linked genes followed by partial overlapping hybridization, we constructed a 210‐kb map encompassing the centromere in chromosome II and a 60‐kb map near the centromere of chromosome I in the fission yeast Schizosaccharomyces pombe which has three chromosomes. Integration of the cloned sequences onto the chromosome and subsequent analyses of tetrads and dyads revealed an ∼50 kb long domain located in the middle of the 210‐kb map, tightly linked to the centromere and greatly reduced in meiotic recombination. This domain contained at least two classes of repetitive sequences. One, designated yn1, was specifically present in a particular chromosome and repeated three times in the 210‐kb map of chromosome II. The other, designated dg, was located in all the centromere regions of three chromosomes. One (dgI) and two (dgIIa, dgIIb) copies of the dg were found in the maps of chromosomes I and II, respectively. The dgIIa and dgIIb were arranged with a 20‐kb interval within the repetitive domain. In the centric region of chromosome III, 3−4 copies of the dg appeared to exist. By determining the nucleotide sequences of dgI and dgIIa, the dg was identified to be 3.8 kb long. The sequence homology was 99% between dgI and dgIIa. These extraordinarily homologous sequences seemed not to be transcribed into RNA nor to be encoding any protein. The larger part of the dg sequence was internally non‐repetitious, a 600‐bp region existed which consisted of stretches of several short repeating units. The structures in or surrounding the centromeres of S. pombe appear to be much more complex than those of the budding yeast Saccharomyces cerevisiae.
Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation

ABSTRACT The mammary epithelium elaborates through hormonally regulated changes in proliferation, migration and differentiation. Non-muscle myosin II (NMII) functions at the interface between contractility, adhesion and signal transduction. It is therefore a plausible regulator of mammary morphogenesis. We tested the genetic requirement for NMIIA and NMIIB in mammary morphogenesis through deletion of the three NMII heavy chain-encoding genes (NMHCIIA, NMHCIIB and NMHCIIC; also known as MYH9, MYH10 and MYH14, respectively) that confer specificity to the complex. Surprisingly, mosaic loss, but not ubiquitous loss, of NMHCIIA and NMHCIIB induced high levels of proliferation in 3D culture. This phenotype was observed even when cells were cultured in basal medium, which does not support tissue level growth of wild-type epithelium. Mosaic loss of NMIIA and NMIIB combined with FGF signaling to induce hyperplasia. Mosaic analysis revealed that the cells that were null for both NMIIA and NMIIB, as well as wild-type cells, proliferated, indicating that the regulation of proliferation is both cell autonomous and non-autonomous within epithelial tissues. This phenotype appears to be mediated by cell–cell contact, as co-culture did not induce proliferation. Mosaic loss of NMIIA and NMIIB also induced excess proliferation in vivo. Our data therefore reveal a role for NMIIA and NMIIB as negative regulators of proliferation in the mammary epithelium. Summary: Deletion of both non-muscle myosin IIA and IIB in a mosaic subset of cells in the mammary epithelium induces tissue growth and proliferation in 3D culture and in vivo.
Spatial density and distribution of choline acetyltransferase immunoreactive cells in human, macaque, and baboon retinas

Whole‐mounted human, macaque, and baboon retinas were labelled with an antiserum to human choline acetyltransferase (ChAT), by the immunoperoxidase technique. Previous work in nonprimate species has shown that these cells correspond to the starburst amacrine cells. Labelled somata were disposed on either side of the inner plexiform layer, and their processes formed two narrow zones within it.
Providing security and privacy in smart house through mobile cloud computing

Smart house allows residents to access appliances and smart grid data to reconfigure its power consumption. This paper aims to provide security and privacy by design in a smart house, isolating appliances from direct Internet access, while allowing external entities to reach power consumption features. Data acquisition, processing, and consumer profiles updates are only possible inside a smart house, using a Mobile Cloud Computing (MCC). MCC enables to reconfigure consumption profile of smart houses, for instance, to avoid a potential blackout. In addition, the proposal improves security and privacy for smart houses, preventing an attacker to remotely control appliances or violating the privacy of residents by monitoring their energy consumption habits. Prototype tests showed the feasibility of our proposal, isolating the appliances and MCC mobiles, besides collecting, processing, and storing 1200 appliances attributes in 15.25 seconds while using only three mobile devices in an MCC.
Biomaterial-based drug delivery systems for the controlled release of neurotrophic factors

This review highlights recent work on the use of biomaterial-based drug delivery systems to control the release of neurotrophic factors as a potential strategy for the treatment of neurological disorders. Examples of neurotrophic factors include the nerve growth factor, the glial cell line-derived neurotrophic factor, the brain-derived neurotrophic factor and neurotrophin-3. In particular, this review focuses on two methods of drug delivery: affinity-based and reservoir-based systems. We review the advantages and challenges associated with both types of drug delivery system and how these systems can be applied to neurological diseases and disorders. While a limited number of affinity-based delivery systems have been developed for the delivery of neurotrophic factors, we also examine the broad spectrum of reservoir-based delivery systems, including microspheres, electrospun nanofibers, hydrogels and combinations of these systems. Finally, conclusions are drawn about the current state of such drug delivery systems as applied to neural tissue engineering along with some thoughts on the future direction of the field.
Effect of body temperature on chondroitinase ABC's ability to cleave chondroitin sulfate glycosaminoglycans

Chondroitinase ABC (Ch'ase ABC) is a bacterial lyase that degrades chondroitin sulfate (CS), dermatan sulfate, and hyaluronan glycosaminoglycans (GAGs). This enzyme has received significant attention as a potential therapy for promoting central nervous system and peripheral nervous system repair based on its degradation of CS GAGs. Determination of the stability of Ch'ase ABC activity at temperatures equivalent to normal (37°C) and elevated (39°C) body temperatures is important for optimizing its clinical usage. We report here data obtained from examining enzymatic activity at these temperatures across nine lots of commercially available protease‐free Ch'ase ABC. CS GAG degrading activity was assayed by using 1) immunohistochemical detection of unsaturated disaccharide stubs generated by digestion of proteoglycans in tissue sections and 2) fluorophore‐assisted carbohydrate electrophoresis (FACE) and/or high‐performance liquid chromatography (HPLC) to separate and quantify unsaturated disaccharide digestion products. Our results indicate that there is a significant effect of lot and time on enzymatic thermostability. Average enzymatic activity is significantly decreased at 1 and 3 days at 39°C and 37°C, respectively. Furthermore, the average activity seen after 1 day was significantly different between the two temperatures. Addition of bovine serum albumin as a stabilizer significantly preserved enzymatic activity at 1 day, but not 3 days, at 39°C. These results show that the CS GAG degrading activity of Ch'ase ABC is significantly decreased with incubation at body temperature over time and that all lots do not show equal thermostability. These findings are important for the design and interpretation of experimental and potential clinical studies involving Ch'ase ABC. © 2007 Wiley‐Liss, Inc.