Miracle-dz/UniFAR-FTUs huggingface dataset:
Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis

Background and aim There is a growing body of evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. In fact, PAI-1 knockout mice are protected from bleomycin-induced pulmonary fibrosis. This study was conducted to determine whether the intrapulmonary administration of small interfering RNA (siRNA) targeting PAI-1 (PAI-1-siRNA) limits the development of bleomycin-induced pulmonary fibrosis. Methods Lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) were stained for PAI-1. The distribution of siRNA in the lung, the PAI-1 level in bronchoalveolar (BAL) fluid and the extent of fibrotic changes in the lung were evaluated following the intranasal administration of PAI-1-siRNA in a mouse model of bleomycin-induced pulmonary fibrosis. The effect of PAI-1-siRNA on the epithelial to mesenchymal transition (EMT) was also evaluated using a mouse lung epithelial cell line, LA-4. Results PAI-1 was overexpressed in the hyperplastic type 2 pneumocytes lining the honeycomb lesions of patients with IPF. The single intranasal instillation of PAI-1-siRNA resulted in the diffuse uptake of siRNA into the epithelial cells lining the dense fibrotic lesions. The repeated administration of PAI-1-siRNA initiated during either the inflammatory or the fibrotic phase into bleomycin-injured mice reduced the PAI-1 level in BAL fluid and limited the accumulation of collagen in the lungs. EMT induced by transforming growth factor β (TGFβ) in LA-4 cells was inhibited by transfection with PAI-1-siRNA. Conclusions The direct suppression of PAI-1 in the lung by the intrapulmonary administration of PAI-1-siRNA attenuated the development and progression of pulmonary fibrosis. The inhibition of EMT may be, at least in part, involved in this effect.
The role of the picoeukaryote Aureococcus anophagefferens in cycling of marine high—molecular weight dissolved organic nitrogen

Environmental evidence suggests that Aureococcus anophagefferens (Pelagophyceae), a eukaryotic picoplankton that blooms in coastal seawaters, can outcompete other organisms because of its ability to use abundant dissolved organic nitrogen (DON). To test this hypothesis, we isolated A. anophagefferens in axenic culture and monitored its growth on high‐molecular weight (HMW) DON collected from sediment pore waters, a putative source for DON in bays where blooms occur. HMW DON originating from pore water had a substantially higher protein content than surface seawater DON. We found that A. anophagefferens could deplete 25–36% of the available nitrogen in cultures with HMW DON as the sole source of nitrogen and that this corresponded well with the protein fraction in pore‐water HMW DON. High rates of cell surface peptide hydrolysis and no detectable N‐acetyl polysaccharide hydrolysis, together with the high percentage of hydrolyzable amino acids compared to hydrolyzable aminosugars present in the HMW DON, pointed to the protein fraction as the more likely source of nitrogen used for growth. Whether or not nitrogen scavenging from protein is a common mechanism in phytoplankton is at present unknown but needs to be investigated.
The LX—T relation and intracluster gas fractions of X-ray clusters

We re-examine the X-ray luminosity–temperature relation using a nearly homogeneous data set of 24 clusters selected for statistically accurate temperature measurements and absence of strong cooling flows. The data exhibit a remarkably tight power-law relation between bolometric luminosity and temperature with a slope 2.88 ± 0.15. With reasonable assumptions regarding cluster structure, we infer an upper limit on fractional variations in the intracluster gas fraction 〈(δ fgas fgas)2〉1/2≤ 15 per cent. A strictly homogeneous Ginga subset of 18 clusters places a more stringent limit of 9 per cent. Imaging data from the literature are employed to determine absolute values of fgas within spheres encompassing density contrasts δc=500 and 200 with respect to the critical density. Comparing binding mass estimates based on the virial theorem (VT) and the hydrostatic β-model (BM), we find a temperature-dependent discrepancy in fgas between the two methods caused by systematic variation of the outer slope parameter β with temperature. Mean values (for H0=50 km s−1 Mpc−1) range from f¯gas=0.10 for cool (T 4 keV) clusters using the BM at δc=200. There is evidence that cool clusters have a lower mean gas fraction than hot clusters, but it is not possible to assess the statistical significance of this effect in the present data set. The T dependence of the intracluster medium (ICM) density structure, coupled with the increase of the gas fraction with T in the VT approach, explains the steepening of the LX–T relation. The small variation about the mean gas fraction within this majority subpopulation of clusters presents an important constraint for theories of galaxy formation and supports arguments against an Einstein–de Sitter universe based on the population mean gas fraction and conventional, primordial nucleosynthesis. The apparent trend of lower gas fractions and more extended atmospheres in low-temperature systems is consistent with expectations of models incorporating the effects of galactic winds on the ICM.
The lived experience of physicians dealing with patient death

Background A growing body of research indicates that physicians suffer high levels of stress, depression and burnout. Related literature has found that physician stress can negatively impact patient care. This study builds upon previous research that found some dying patients experienced ‘iatrogenic suffering’ caused by the way physicians communicated with them regarding terminal diagnoses and palliative treatment. The goal of this research was to explore physicians’ experiences of dealing with patient death in order to understand how such experiences affect them and their communication with patients. Methods This study used qualitative methods to conduct and analyse 10 individual, semistructured interviews with senior physicians from several specialty areas at a large, tertiary care hospital. The resulting themes were validated using member checks and expert review. Results This article presents five essential themes that provide a concise description of the lived experience of patient death for these physicians. Interpretation: These themes indicate that physicians can experience very strong and lasting emotional reactions to some patient deaths, and also that patient death can elicit intense experiences related to professional responsibility and competence. A key finding is the description of a complex process of managing the balance between personal and professional reactions in the face of patient death. The implication is that difficulties negotiating this balance may lead to unintended lapses in compassion and suboptimal outcomes in patient care.
Cognitive-behavioural stimulation protocol for severely brain-damaged patients in the post-acute stage in developmental age

Purpose. To present a cognitive-behavioural stimulation (CBS) protocol designed to help severely damaged patients in the early post-acute stage by describing the underlying methodology and assessing its efficacy compared to traditional rehabilitation methods. This protocol combines multisensory stimulation and cognitive-behavioural techniques to elicit and intensify the occurrence of adaptive responses and reduce maladaptive behavioural patterns. Methods. A control group and an experimental group – both evaluated with the Levels of Cognitive Functioning Assessment Scale (LOCFAS) – were compared at the beginning of the rehabilitation programme and at the end of it. The control group consisting of patients assessed and treated before receiving the CBS protocol was enrolled in a traditional rehabilitation programme (only physical therapy and speech therapy). Besides the traditional therapy, the experimental group also received the CBS protocol. Results. Patients on the CBS protocol show a greater improvement and are therefore more responsive than the control group after the 16-week remediation programme. The mean LOCFAS improvement of the experimental group is more marked during the first month of rehabilitation and is associated to the entry LOCFAS level, while in the control group the improvement on LOCFAS is considered to be ‘spontaneous’ and is associated to the aetiology of the brain damage. Conclusions. Our results show a better initial outcome for patients receiving the CBS protocol.
Anticoagulation in patients with non-valvular atrial fibrillation: an evaluation of stability and early factors that predict longer-term stability on warfarin in a large UK population

ABSTRACT Objective: To determine the proportion of patients with non-valvular atrial fibrillation (NVAF) treated with warfarin that achieved a 6‐month period within the target INR range (stability). To then evaluate any associations between stability and outcome and to determine whether stability can be predicted by clinical factors at an early stage in warfarin treatment. Methods: This study was a record linkage study in 1513 patients with NVAF treated with warfarin for a minimum of 6‐months, carried out in a large UK population. The main outcome measures were stability (defined as six months within the target INR range [2.0–3.0]), thromboembolic and bleeding event rates and mortality. Secondary outcome measures were the predictive value of baseline characteristics and other treatment variables. Results: Stability was achieved in 52% of the study group. Standardised mean survival was significantly higher in the group who achieved stability (∆ = 16.91 months, p < 0.001) with a hazard ratio of 4.36 ( p < 0.001). The stable group had a lower rate of both thromboembolic events (0.8% vs. 2.3% per patient year) and bleeds recorded on inpatient diagnoses (0.4% vs. 1.2% per patient year). Failure to achieve stable control was associated with age (Odds Ratio [OR] 1.011 (95% Confidence Interval [CI] 1.001–1.021)) and morbidity at baseline (OR 1.015; 95% CI 1.007–1.022). An increase in mean time between visits (OR 0.939; 95% CI 0.926–0.952) and the percentage time in range (OR 0.889; 95% CI 0.879–0.900) was associated with a decrease in the chance of instability. Greater variability in INR was also associated with a failure to achieve stability (OR 1.518; 95% CI 1.427–1.615). Receiver Operator Characteristic (ROC) analysis using data from the first three months of treatment demonstrated good discrimination of stability using age and morbidity at baseline and percentage time in range and frequency of visits during the first three months of treatment (area under curve [AUC] 0.780; standard error [SE] 0.012; 95% CI 0.757–0.803). Conclusions: Many patients never achieved a period of 6‐months stability and were at increased risk of thromboembolic events and bleeds. Age, morbidity at baseline and variability of INR control in the first three months could be used to predict instability using warfarin. This study infers that patients should be treated more intensively in the early stages of warfarinisation in order to improve outcome.
Talker-specific influences on phonetic category structurea )

A primary goal for models of speech perception is to describe how listeners achieve reliable comprehension given a lack of invariance between the acoustic signal and individual speech sounds. For example, individual talkers differ in how they implement phonetic properties of speech. Research suggests that listeners attain perceptual constancy by processing acoustic variation categorically while maintaining graded internal category structure. Moreover, listeners will use lexical information to modify category boundaries to learn to interpret a talker’s ambiguous productions. The current work examines perceptual learning for talker differences that signal well-defined, unambiguous category members. Speech synthesis techniques were used to differentially manipulate talkers’ characteristic productions of the stop voicing contrast for two groups of listeners. Following exposure to the talkers, internal category structure and category boundary were examined. The results showed that listeners dynamically adjusted internal category structure to be centered on experience with the talker’s voice, but the category boundary remained fixed. These patterns were observed for words presented during training as well as novel lexical items. These findings point to input-driven constraints on functional plasticity within the language architecture, which may help to explain how listeners maintain stability of linguistic knowledge while simultaneously demonstrating flexibility for phonetic representations. VC 2015 Acoustical Society of America. [http://dx.doi. org/10.1121/1.4927489]
Fine needle aspiration biopsy of thyroid nodules

BACKGROUND Fine needle aspiration biopsy (FNA) is a routine diagnostic technique for evaluating thyroid nodules. Many reports in adults consider that FNA is superior to thyroid ultrasonography (USG) and radionuclide scanning (RS). Only five studies have been published on FNA of childhood thyroid nodules. AIMS To investigate the reliability of FNA in the evaluation and management of thyroid nodules, and compare the results of FNA, USG, and RS with regard to final histopathological diagnosis. METHODS FNA was performed in 46 children with thyroid nodules after USG and RS examination. We investigated the sensitivity, specificity, accuracy, and positive and negative predictive values of USG, RS, and FNA in their management. RESULTS Six patients who had malignant or suspicious cells on FNA examination underwent immediate surgery. The other 40 patients received medical treatment according to their hormonal status. Fifteen of these nodules either disappeared or decreased in number and/or size. Surgery was performed in 25 patients who did not respond to therapy. Statistical analysis revealed sensitivity, specificity, accuracy, and positive and negative predictive values respectively as follows: 60%, 59%, 59%, 15%, and 92% for USG; 30%, 42%, 39%, 12%, and 68% for SC; 100%, 95%, 95%, 67%, and 100% for FNAB. CONCLUSION FNAB is as reliable in children as in adults for definitive diagnosis of thyroid nodules. Using this technique avoids unnecessary thyroid surgery in children.
The dynamic self: Exploring the critical role of the default mode network in self-referential processing

Investigation of the neural correlates of the self has implicated a network of brain regions including the medial prefrontal cortex (MPFC), posterior cingulate (PCC), precuneus (pC), and inferior parietal lobule (IPL). At the same time, recent neuroimaging work has identified the Default Mode Network (DMN), a network of brain regions that are highly active at ‘rest’ (without an active cognitive task). While the functional significance of the DMN remains unknown, converging evidence suggests that the DMN might be critical for self-referential processing (e.g., introspection). In this dissertation, I tested this hypothesis using a lesion approach. In the first experiment, I examined the critical role of the DMN hubs (MPFC, IPL) in autobiographical memory (AM) retrieval. I predicted that if the DMN hubs were critical for AM, then lesions to either the MPFC or IPL should result in AM retrieval impairments. I tested this prediction using the Iowa Autobiographical Memory Questionnaire (IAMQ), a questionnaire that assessed retrograde AM retrieval. In support of the prediction, lesions to the MPFC and IPL were associated with significant AM retrieval impairments. While not predicted, AM retrieval deficits were also associated with lesions in medial and lateral temporal cortices, regions also considered part of the DMN. In the second experiment, I tested the critical role of the DMN hubs in the self-reference effect (SRE), a well-known memory advantage conferred by self-related processing. I predicted that if the DMN hubs were critical for the SRE, then damage to the MPFC or IPL should diminish the effect. I used a standard personality trait judgment paradigm to test this prediction. In partial support of the prediction, I found that damage to the MPFC abolished the SRE with a “self” specific deficit. While IPL damage was associated with a diminished SRE, the effects were not significant. In the
Prospective multicentre randomized controlled trial to evaluate factors influencing the success rate of office diagnostic hysteroscopy.

BACKGROUND Diagnostic hysteroscopy is not widely performed in the office setting, one of the reasons being the discomfort produced by the procedure. This randomized controlled trial was performed to evaluate the effects of instrument diameter, patient parity and surgeon experience on the pain suffered and success rate of the procedure. METHODS Patients were randomly assigned to undergo office diagnostic hysteroscopy either with 5.0 mm conventional instruments (n=240) or with 3.5 mm mini-instruments (n=240). Procedures were stratified according to patient parity and surgeon's previous experience. The pain experienced during the procedure (0-10), the quality of visualization of the uterine cavity (0-3) and the complications were recorded. The examination was considered successful when the pain score was <4, visualization score was >1 and no complication occurred. RESULTS Less pain, better visualization and higher success rates were observed with mini-hysteroscopy (P <0.0001, P <0.0001 and P <0.0001, respectively), in patients with vaginal deliveries (P <0.0001, P <0.0001 and P <0.0001, respectively) and in procedures performed by experienced surgeons (P=0.02, P=NS and P=NS, respectively). The effects of patient parity and surgeon experience were no longer important when mini-hysteroscopy was used. CONCLUSIONS Our data demonstrate the advantages of mini-hysteroscopy and the importance of patient parity and surgeon experience, suggesting that mini-hysteroscopy should always be used, especially for inexperienced surgeons and when difficult access to the uterine cavity is anticipated. They indicate that mini-hysteroscopy can be offered as a first line office diagnostic procedure.
Ferrocene Orientation Determined Intramolecular Interactions Using Energy Decomposition Analysis

Two very different quantum mechanically based energy decomposition analyses (EDA) schemes are employed to study the dominant energy differences between the eclipsed and staggered ferrocene conformers. One is the extended transition state (ETS) based on the Amsterdam Density Functional (ADF) package and the other is natural EDA (NEDA) based in the General Atomic and Molecular Electronic Structure System (GAMESS) package. It reveals that in addition to the model (theory and basis set), the fragmentation channels more significantly affect the interaction energy terms (ΔE) between the conformers. It is discovered that such an interaction energy can be absorbed into the pre-partitioned fragment channels so that to affect the interaction energies in a particular conformer of Fc. To avoid this, the present study employs a complete fragment channel—the fragments of ferrocene are individual neutral atoms. It therefore discovers that the major difference between the ferrocene conformers is due to the quantum mechanical Pauli repulsive energy and orbital attractive energy, leading to the eclipsed ferrocene the energy preferred structure. The NEDA scheme further indicates that the sum of attractive (negative) polarization (POL) and charge transfer (CL) energies prefers the eclipsed ferrocene. The repulsive (positive) deformation (DEF) energy, which is dominated by the cyclopentadienyle (Cp) rings, prefers the staggered ferrocene. Again, the cancellation results in a small energy residue in favour of the eclipsed ferrocene, in agreement with the ETS scheme. Further Natural Bond Orbital (NBO) analysis indicates that all NBO energies, total Lewis (no Fe) and lone pair (LP) deletion all prefer the eclipsed Fc conformer. The most significant energy preferring the eclipsed ferrocene without cancellation is the interactions between the donor lone pairs (LP) of the Fe atom and the acceptor antibond (BD*) NBOs of all C–C and C–H bonds in the ligand, LP(Fe)-BD*(C–C & C–H), which strongly stabilizes the eclipsed (D5h) conformation by −457.6 kcal·mol−1.
Characterizing pharmacological ligands to study the long‐chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4

The free fatty acid receptors (FFA) 1 (previously designated GPR40) and FFA4 (previously GPR120) are two GPCRs activated by saturated and unsaturated longer‐chain free fatty acids. With expression patterns and functions anticipated to directly or indirectly promote insulin secretion, provide homeostatic control of blood glucose and improve tissue insulin sensitivity, both receptors are being studied as potential therapeutic targets for the control of type 2 diabetes. Furthermore, genetic and systems biology studies in both humans and mouse models link FFA4 receptors to diabetes and obesity. Although activated by the same group of free fatty acids, FFA1 and FFA4 receptors are not closely related and, while the basis of recognition of fatty acids by FFA1 receptors is similar to that of the short‐chain fatty acid receptors FFA2 and FFA3, the amino acid residues involved in endogenous ligand recognition by FFA4 receptors are more akin to those of the sphingosine 1 phosphate receptor S1P1. Screening and subsequent medicinal chemistry programmes have developed a number of FFA1 receptor selective agonists that are effective in promoting insulin secretion in a glucose concentration‐dependent manner, and in lowering blood glucose levels. However, the recent termination of Phase III clinical trials employing TAK‐875/fasiglifam has caused a setback and raises important questions over the exact nature and mechanistic causes of the problems. Progress in the identification and development of highly FFA4 receptor‐selective pharmacological tools has been less rapid and several issues remain to be clarified to fully validate this receptor as a therapeutic target. Despite this, the ongoing development of a range of novel ligands offers great opportunities to further unravel the contributions of these receptors.