Miracle-dz/UniFAR-FTUs huggingface dataset:
The dose of inhaled corticosteroids in patients with COPD: when less is better

Background: The use of inhaled corticosteroids (ICS) in combination with bronchodilators in patients with COPD has been shown to decrease the rate of disease exacerbations and to improve the lung function and patients’ quality of life. However, their use has also been associated with an increased risk of pneumonia. Materials and methods: We have reviewed existing clinical evidence on the risks and benefits of ICS in COPD, including large randomized clinical trials, meta-analyses, and clinical reviews. Results: A large body of evidence supports the clinical benefits of ICS in patients with COPD in terms of exacerbations, symptoms, lung function, and quality of life. The incidence of adverse events related to ICS, including pneumonia, varies strongly among the studies and seems to be dose dependent, with recent well-designed, large studies on low-dose ICS reporting similar safety profiles in ICS and non-ICS groups. Conclusion: The benefits of ICS in COPD continue to outweigh the risks, especially when lower ICS doses are employed. Given that the data on ICS withdrawal in COPD are scarce and conflicting, we argue that using reduced doses of ICS could be an optimal strategy to manage patients with COPD.
Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk?

Abstract Low-density lipoproteins (LDLs) are susceptible to structural modifications by oxidation, particularly the small dense LDL particles. The formation of lipid peroxidation derivates, such as thiobarbituric reactive substances, conjugated dienes, lipid hydroperoxides, and aldehydes, is associated with changes in apolipoprotein conformation and affects the functional properties of LDLs. Oxidized LDL (oxLDL) formation in the subendothelial space of the arterial wall is a key initiating step in atherosclerosis because it contributes to foam cell generation, endothelial dysfunction, and inflammatory processes. In the last decade, immunoassays were developed using monoclonal antibodies against oxidation-dependent epitopes of LDL which made it possible to directly measure oxLDL in the circulation. Increased circulating oxLDL concentrations have been related to cardiovascular disease in some studies, although not always independently after adjustment of classical lipid markers. The Asklepios Study, investigating 2524 healthy middle-aged subjects, showed that circulating oxLDL is affected by many biological and lifestyle factors, as well as (generalized) subclinical atherosclerosis. Clin Chem Lab Med 2009;47:128–37.
Effects of musical training and hearing loss on pitch discrimination

Effects of musical training and hearing loss on pitch discrimination Our ability to perceive the pitch of complex sounds is essential for melody perception and for our enjoyment of music. It also plays an important role in speech perception to convey intonation and sometimes meaning, e.g., in tonal languages, and greatly helps segregation of competing sound sources. Humans are able to discriminate very small changes in the pitch of complex harmonic sounds, with fundamental frequency difference limens (F0DLs) that can be smaller than 1% of the fundamental frequency (F0). However, performance in such pitch discrimination tasks is known to depend on the harmonic content of the sound and whether the harmonics are resolved by the auditory frequency analysis operated by cochlear processing. F0DLs are also heavily influenced by the amount of musical training received by the listener and by the spectrotemporal auditory processing deficits that often accompany sensorineural hearing loss. This paper reviews the latest evidence for how musical training and hearing loss affect pitch discrimination performance, based on behavioral F0DL experiments with complex tones containing either resolved or unresolved harmonics, carried out in listeners with different degrees of hearing loss and musicianship. A better understanding of the interaction between these two factors is crucial to determine whether auditory training based on musical tasks or targeted towards specific auditory cues may be useful to hearing-impaired patients undergoing hearing rehabilitation.
RANDOMISED CONTROLLED TRIAL TO DETERMINE THE ROLE OF FIBULAR FIXATION IN BOTH DISTAL THIRD TIBIAL DIAPHYSIS AND FIBULAR FRACTURES

Fixation of Distal third tibial diaphysis fractures poses unique challenges in terms of selection of appropriate implants and reduction of the fracture. Distal tibial diaphyseal fractures associated with fibular fractures produce valgus malalignment at the fracture site. Fibular plating has been classically recommended before tibial fixation citing improved alignment of the fracture along with maintenance of length, ensuring proper reduction of the tibial fracture. However, it is not exempt from complications of surgical procedure and recent literatures have equally favoured tibial fixations without fibular plating in such distal third diaphyseal fractures. So, we have tried to compare the outcome of tibia fixation with or without fibular plating in distal third diaphyseal fractures. This is a randomized controlled trial involving 66 cases treated with (group A) or without (group B) fibular fixations. Tibial fixation was done with distal tibial metaphyseal locking plate or intramedullary interlocking nail system. Patients were followed up at 6 weeks, 12 weeks and 6 months. Clinical and radiological union was assessed at 6 months follow up, and Johner and Wruhs score was calculated. 11 patients were lost to follow up. In both groups, there was no excellent or poor result. Group A had good results in 22 out of 26 patients (84.6%) and 4 had fair results (15.3%). Group B had good results in 20 out of 29 patients (68.9%) and fair in 9 out of 29 patients (31%). There was no significant difference in tibial malalignment (valgus angulation) between the two groups.
Use of idarucizumab in reversing dabigatran anticoagulant effect: a critical appraisal

: Use of non-vitamin K antagonist oral anticoagulants is spreading in the real world. Despite that, a strong need for antidotes/reversal agents is still reported by several physicians. Idarucizumab is a humanized monoclonal antibody fragment that binds specifically to dabigatran. Idarucizumab was approved in 2015 by the US Food and Drugs Administration and European Medicines Agency for reversal of anticoagulation activity in dabigatran-treated patients. This review briefly summarizes the experimental evidence about effectiveness and safety of idarucizumab. Furthermore, we review the current recommendations and experts’ point of view about the use of antidotes/reversal agents in patients reporting a major bleeding event.
Edinburgh Research Explorer Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis

Background: While dietary fat has been established as a risk factor for colorectal cancer (CRC), associations between fatty acids (FAs) and CRC have been inconsistent. Using Mendelian randomisation (MR), we sought to evaluate associations between polyunsaturated (PUFA), monounsaturated (MUFA) and saturated FAs (SFAs) and CRC risk. Methods: We analysed genotype data on 9254 CRC cases and 18,386 controls of European ancestry. Externally weighted polygenic risk scores were generated and used to evaluate associations with CRC per one standard deviation increase in genetically deﬁned plasma FA levels. Results: Risk reduction was observed for oleic and palmitoleic MUFAs (OR OA Z 0.77, 95% CI: 0.65 e 0.92, P Z 3.9 (cid:2) 10 (cid:3) 3 ; OR POA Z 0.36, 95% CI: 0.15 e 0.84, P Z 0.018). PUFAs linoleic and arachidonic acid had negative and positive associations with CRC respectively (OR LA Z 0.95, 95% CI: 0.93 e 0.98, P Z 3.7 (cid:2) 10 (cid:3) 4 ; OR AA Z 1.05, 95% CI: 1.02 e 1.07,
Complementary codes for odor identity and intensity in olfactory cortex

The ability to represent both stimulus identity and intensity is fundamental for perception. Using large-scale population recordings in awake mice, we find distinct coding strategies facilitate non-interfering representations of odor identity and intensity in piriform cortex. Simply knowing which neurons were activated is sufficient to accurately represent odor identity, with no additional information about identity provided by spike time or spike count. Decoding analyses indicate that cortical odor representations are not sparse. Odorant concentration had no systematic effect on spike counts, indicating that rate cannot encode intensity. Instead, odor intensity can be encoded by temporal features of the population response. We found a subpopulation of rapid, largely concentration-invariant responses was followed by another population of responses whose latencies systematically decreased at higher concentrations. Cortical inhibition transforms olfactory bulb output to sharpen these dynamics. Our data therefore reveal complementary coding strategies that can selectively represent distinct features of a stimulus. DOI: http://dx.doi. org/10.7554/eLife.22630. 001
A Systems-Level Framework for Drug Discovery Identifies Csf1R As A Novel Anti-Epileptic Drug Target

The identification of mechanistically novel drug targets is highly challenging, particularly for diseases of the central nervous system. To address this problem we developed and experimentally validated a new computational approach to drug target identification that combines gene-regulatory information with a causal reasoning framework (“causal reasoning analytical framework for target discovery” – CRAFT). Starting from gene expression data, CRAFT provides a predictive functional genomics framework for identifying membrane receptors with a direction-specified influence over network expression. As proof-of-concept we applied CRAFT to epilepsy, and predicted the tyrosine kinase receptor Csf1R as a novel therapeutic target for epilepsy. The predicted therapeutic effect of Csf1R blockade was validated in two pre-clinical models of epilepsy using a small molecule inhibitor of Csf1R. These results suggest Csf1R blockade as a novel therapeutic strategy in epilepsy, and highlight CRAFT as a systems-level framework for predicting mechanistically new drugs and targets. CRAFT is applicable to disease settings other than epilepsy.
Key success factors in managing the visitors' experience at the Klein Karoo National Arts Festival

The event industry and more specifically arts festivals may be seen as one of the fastest growing sectors in the tourism industry of South Africa. However, limited research has been done to identify the factors visitors to an arts festival view as important to achieve a unique festival experience. Therefore the purpose of this research is to identify the Key Success Factors (KSFs) of managing the visitors’ experience at one of South Africa’s most popular Afrikaans arts festival namely Klein Karoo National Arts Festival (KKNK). To achieve this goal a questionnaire survey (N=443) was conducted where after a factor analysis was performed to identify the following seven KSFs: Safety and Personnel, Marketing and Accessibility, Venues, Accommodation and Ablution, General aspects and Social impact, Parking and Restaurants and Shows and Stalls. The results showed that visitors to the KKNK regard the wide variety of quality and affordable shows and products at stalls, friendly informed staff, visible emergency and security services and an adequate amount of air-conditioned venues with good technical aspects as important to satisfy their needs and providing them with a unique festival experience. Results also showed that Shows and Stalls and Parking and Restaurants could be regarded as unique KSFs in terms of arts festivals in South Africa.
Planning through projects : moving from master planning to strategic planning 30 cities

"Planning Through Projects" shows how the shift from master planning to strategic planning through large urban projects is a worldwide process affecting all countries, and it highlights the impact that such large projects have on urban governance. The book presents thirty megacities from all over the world, considering their socioeconomic and environmental context, and the plans and strategies implemented. The global scope, the combination of theory and practice, and the many examples, plans, and illustrations make this book an excellent reference for teachers, students, and professionals working in urban planning and management. The book includes 30 comprehensive case studies from major cities all over the world: Beijing, Bilbao, Bogota, Buenos Aires, Caracas, Cordoba, Daego, Fukoaka, Glasgow, Hsinshu, La Plata, Liverpool, Lusaka, Mexico City, Montevideo, Ningbo, Panama, Paris, Pretoria, Taipei, The Hague, Tokyo, Rio de Janeiro, Rotterdam, Santiago, San Salvador, Sao Paulo, Singapore, Shanghai, and Valparaiso. "
Dynamic FOV visible light communications receiver for dense optical networks

This study explores how the field-of-view (FOV) of a visible light communications (VLCs) receiver can be manipulated to realise the best signal-to-noise ratio (SNR) while supporting device mobility and optimal access point (AP) selection. The authors propose a dynamic FOV receiver that changes its aperture according to receiver velocity, location, and device orientation. The D-FOV technique is evaluated through modelling, analysis, and experimentation in an indoor environment comprised of 15 VLC APs. The proposed approach is also realised as an algorithm that is studied through analysis and simulation. The results of the study indicate the efficacy of the approach including a 3X increase in predicted SNR over static FOV approaches based on measured received signal strength in the testbed. Additionally, the collected data reveal that D-FOV increases effectiveness in the presence of noise. Finally, the study describes the tradeoffs among the number of VLC sources, FOV, user device velocity, and SNR as a performance metric.
Population Immunity against Serotype-2 Poliomyelitis Leading up to the Global Withdrawal of the Oral Poliovirus Vaccine: Spatio-temporal Modelling of Surveillance Data

Background Global withdrawal of serotype-2 oral poliovirus vaccine (OPV2) took place in April 2016. This marked a milestone in global polio eradication and was a public health intervention of unprecedented scale, affecting 155 countries. Achieving high levels of serotype-2 population immunity before OPV2 withdrawal was critical to avoid subsequent outbreaks of sero-type-2 vaccine-derived polioviruses (VDPV2s). In August 2015, we estimated vaccine-induced population immunity against serotype-2 poliomyelitis for 1 January 2004–30 June 2015 and produced forecasts for April 2016 by district in Nigeria and Pakistan. Population immunity was estimated from the vaccination histories of children < 36 mo old identified with non-polio acute flaccid paralysis (AFP) reported through polio surveillance, information on immunisation activities with different oral poliovirus vaccine (OPV) formulations, and serotype-specific estimates of the efficacy of these OPVs against poliomyelitis. District immunity estimates were spatio-temporally smoothed using a Bayesian hierarchical framework. Coverage estimates for immunisation activities were also obtained, allowing for heterogeneity
A note on the independence of central banks in the Czech Republic, Hungary and Poland

This essay evaluates the legal independence of central banks in three Eastern European countries: the Czech Republic, Hungary and Poland. It provides a descriptive account of monetary policy making in these countries and interprets the relevant central bank charters in light of arguments for central bank independence. Information found in the legal documents is summarized in quantitative indices. The main finding is that the three central banks exhibit a similar degree of legal independence, which does not differ from that of the Bundesbank. Keywords; central bank independence, transition in Eastern Europe
A skin disease, a blood disease or something in between? An exploratory focus group study of patients' experiences with porphyria cutanea tarda*

Porphyria cutanea tarda (PCT) is characterized by fragile skin with blistering on sun‐exposed areas. Symptoms typically develop in late adulthood and can be triggered by iron overload, alcohol intake, oestrogens and various liver diseases. Treatment consists of phlebotomy to reduce iron, or increasing urinary porphyrin excretion by administering chlorochin. To optimize patient care, health personnel need to understand the subjective experiences of PCT.
Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care

Purpose: To assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients’ knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY. Patients and methods: New or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye enrolled based on $ 1 of the following at-risk criteria for glaucoma: African Americans $ 40 years of age, Whites $ 50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients’ CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2–4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar’s test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized. Results: At follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline ( P # 0.01 for all questions). Those who were unemployed (odds ratio = 0.63, 95% confidence interval = 0.42–0.95, P = 0.026) or had lower education (odds ratio = 0.55, 95% confidence interval = 0.29–1.02, P = 0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level charac teristics. Ninety-eight percent (n = 501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n = 326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%). Conclusion: Improved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness. problem, somewhat of problem,
A Phylogenomic Study Quantifies Competing Mechanisms for Pseudogenization in Prokaryotes

Background Pseudogenes are non-functional sequences in the genome with homologous sequences that are functional (i.e. genes). They are abundant in eukaryotes where they have been extensively investigated, while in prokaryotes they are significantly scarcer and less well studied. Here we conduct a comprehensive analysis of the evolution of pseudogenes in prokaryotes. For this analysis we consider a broad range of bacteria, but also focus on the leprosy pathogen Mycobacterium leprae, which contains an unusually large number of pseudogenes which comprise approximately 40% of its entire genome. Results We have developed an informatics-based approach to characterize the evolution of pseudogenes. This approach combines tools from phylogenomics, genomics, and transcriptomics. The results we obtain suggest the presence of two mechanisms for pseudogene formation: failed horizontal gene transfer events and disruption of native genes. Conclusions We conclude that while in most bacteria the former is most likely responsible for the majority of pseudogenization events, in mycobacteria, and in particular in M. leprae with its exceptionally high pseudogene numbers, the latter predominates. We believe that our study sheds new light on the evolution of pseudogenes in bacteria, by utilizing new methodologies that are applied to the unusually abundant M. leprae pseudogenes and their orthologs. As such, we anticipate that it will be of broad interest to both evolutionary biologists as well as microbiologists.
The association of hematologic inflammatory markers with atherogenic index in type 2 diabetic retinopathy patients

Background: Atherogenic dyslipidemia is particularly common in people with type 2 diabetes (DM2). Platelets from patients with DM2 have increased reactivity and baseline activation. The aim of the present study is to evaluate the relationship between atherogenic index and hematologic inflammatory markers and to evaluate the relationship between these parameters and associated variables in diabetic retinopathy (DR) patients. Methods: The medical records of all patients admitted to the eye clinic between January and December 2014 were evaluated systematically. Laboratory parameters of 278 outpatients with DM2 diagnosed after the age of 30 years and 107 healthy subjects were analyzed. Results: The DM2 + DR group consisted of 120 patients (47 males and 73 females; mean age 59.8 ± 9.2 years). The DM2 without DR group consisted of 158 patients (59 males and 99 females; mean age 57.3 ± 12.2 years). Mean platelet volume, platelet distribution width (PDW), platelet– lymphocyte (P/L) ratio, triglycerides, and atherogenic index were higher in DM2 patients than in control patients, but there was no difference between the DM2 + DR and the DM2 without DR groups. Only P/L ratio was different in the DM2 + DR patients compared to the DM2 without DR patients. Hemoglobin A1c levels correlated very weakly with the mean platelet volume, PDW, P/L ratio, and the red cell distribution width. The atherogenic index was very weakly correlated with the P/L ratio, PDW, and red cell distribution width. Conclusion: Dyslipidemia-induced inflammation contributes to pathological processes that lead to retinopathy in DR patients.
Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial START (Strategic Timing of AntiRetroviral Treatment) Study

Background. The Strategic Timing of AntiRetroviral Treatment (START) trial demonstrated that immediate (at CD4+ >500 cells/µL) vs deferred (to CD4+ <350 cells/µL or AIDS) antiretroviral therapy (ART) initiation reduced risk for AIDS and serious non-AIDS (SNA). We investigated associations of inflammation, coagulation, and vascular injury biomarkers with AIDS, SNA or death, and the effect of immediate ART initiation. Methods. Biomarkers were measured from stored plasma prior to randomization and at month 8. Associations of baseline biomarkers with event risk were estimated with Cox regression, pooled across groups, adjusted for age, gender, and treatment group, and stratified by region. Mean changes over 8 months were estimated and compared between the immediate and deferred ART arms using analysis of covariance models, adjusted for levels at entry. Results. Baseline biomarker levels were available for 4299 START participants (92%). Mean follow-up was 3.2 years. Higher levels of IL-6 and D-dimer were the only biomarkers associated with risk for AIDS, SNA or death, as well as the individual components of SNA and AIDS events (HRs ranged 1.37–1.41 per 2-fold higher level), even after adjustment for baseline CD4+ count, HIV RNA level, and other biomarkers. At month 8, biomarker levels were lower in the immediate arm by 12%–21%. Conclusions. These data, combined with evidence from prior biomarker studies, demonstrate that IL-6 and D-dimer consistently predict clinical risk across a broad spectrum of CD4 counts for those both ART-naïve and treated. Research is needed to identify disease-modifying treatments that target inflammation beyond the effects of ART.