Miracle-dz/UniFAR-FTUs huggingface dataset:
Sickle Cell Disease: Current Challenges

Sickle cell disease (SCD) is one of the most common monogenic diseases worldwide. Although there have been some advances in the management of SCD, much remains to be learned about the mechanisms underlying the wide phenotypic diversity of the disease. In resource poor countries, basic facilities for diagnosis and management are lacking, systematic screening is not common practice, and diagnosis is made late. Common and important morbidities associated with SCD are vaso-occlusive episodes, infections, acute chest syndrome, stroke and hip necrosis. These morbidities are often not managed effectively due to lack of proper infrastructure, expertise, and economical burden. Inadequate laboratory facilities and prenatal diagnostic services hamper proper management of disease complications as well as prevention. Newborn screening is yet to be implemented at national level in countries like India. Population screening programs are not universally undertaken, and some of the diagnostic strategies used have limitations. Advanced therapeutics like bone marrow transplantation are expensive, and gene therapy and stem cell therapy are still at an experimental stage. Emphasis should be placed on early counseling, newborn screening, anti-microbial prophylaxis, vaccination against infections and training of healthcare workers, patients and caregivers. Natural history of sickle cell disease in specific geographic areas like Africa and India is still unknown, where infections, malaria and malnutrition are key factors affecting the outcome. Further, in these countries, management guidelines used have been largely extrapolated from resourceful countries where most of the research has been done. There is need to develop tailor made guidelines for specific countries and areas. Global burden of SCD is rising, highlighting the need to develop specific prevention and management related national policies for appropriate public health planning. In resource poor countries where SCD is a major public health concern, basic facilities for management are usually not available, systematic screening is not common practice and diagnosis is usually made late, when patients present with severe complications. This article highlights the challenges faced at all levels including patients, relatives, health care personnel, international health organizations, and government health policy makers.
The Cooking Effect on Two Edible Mushrooms in Anatolia : Fatty Acid Composition , Total Bioactive Compounds , Antioxidant and Anticholinesterase Activities

The effects of baking practices on the fatty acid a n bioactivity of edible mushrooms; namely, Lactarius delicious and Ramaria flava, naturally growing in Anatolia were investigated. Each mushroom species was divided into two parts and one of the parts was baked. Both baked and unbaked materials were extra cted with hexane and methanol, successively. The fatty a cid contents of baked and unbaked extracts of both species were carried out by GC and GC-MS analytical techniq ues. In the unbaked extracts palmitic acid (9.7-14. 43%), stearic acid (41.41-6.68%), oleic acid (25.94-47.12 %) and linoleic acid (22.85-9.78%) were identified as major fatty acids, respectively. In the baked extracts, h owever, palmitic acid (7.92-19.12%), stearic acid ( 49.94-6.23%), oleic acid (18.07-45.13%) and linoleic acid (23.369.25%) were identified as major fatty acids, as wel l. The antioxidative effect of the extracts of baked and u baked mushroom species was also determined by usin g four complimentary assays. In addition, the extracts and the major fatty acids were also evaluated for anticholinesterase activity against acetylcholinest erase (AChE) and butyrylcholinesterase (BChE) which are the chief enzymes of Alzheimer’s disease. The baked met hanol extract of R. flava showed the highest activity in DPPH scavenging, ABTS scavenging and BChE assays, w hile the unbaked hexane extract of R. flava exhibited the best lipid peroxidation inhibition activity. In conclusion, baking proved to have influence in nut ritional values and bioactivity properties of L. delicious and R. flava. The nutrient concentration and bioactivities of L. delicious were decreased when baked; however, baked R. flava proved to have higher nutrient concentrations and higher bioactivities than unbaked samples.
Widespread phenotypic and genetic divergence along altitudinal gradients in animals

Altitudinal gradients offer valuable study systems to investigate how adaptive genetic diversity is distributed within and between natural populations and which factors promote or prevent adaptive differentiation. The environmental clines along altitudinal gradients tend to be steep relative to the dispersal distance of many organisms, providing an opportunity to study the joint effects of divergent natural selection and gene flow. Temperature is one variable showing consistent altitudinal changes, and altitudinal gradients can therefore provide spatial surrogates for some of the changes anticipated under climate change. Here, we investigate the extent and patterns of adaptive divergence in animal populations along altitudinal gradients by surveying the literature for (i) studies on phenotypic variation assessed under common garden or reciprocal transplant designs and (ii) studies looking for signatures of divergent selection at the molecular level. Phenotypic data show that significant between‐population differences are common and taxonomically widespread, involving traits such as mass, wing size, tolerance to thermal extremes and melanization. Several lines of evidence suggest that some of the observed differences are adaptively relevant, but rigorous tests of local adaptation or the link between specific phenotypes and fitness are sorely lacking. Evidence for a role of altitudinal adaptation also exists for a number of candidate genes, most prominently haemoglobin, and for anonymous molecular markers. Novel genomic approaches may provide valuable tools for studying adaptive diversity, also in species that are not amenable to experimentation.
Finding frames: new ways to engage the UK public in global poverty

The aim of the study was to explore the potential for frames theory to be used as a practical tool to re-engage the UK public in global poverty. In exploring the uses of frames theory, we have built on work by Tom Crompton at WWF-UK, who began the task of linking values to frames and thereby suggesting new ways forward for engaging the public in environmental issues and actions. An important finding from his Common Cause paper is that there is a common set of values that can motivate people to tackle a range of ‘bigger than self’ problems, including the environment and global poverty. The implication is that large coalitions can – and must – be built across third- sector organisations to bring about a values change in society. This report responds to that call. The basic argument of this paper is that there is a problem in terms of the UK public’s levels of engagement with global poverty. Simply put, people in the UK understand and relate to global poverty no differently now than they did in the 1980s. This is the case despite massive campaigns such as the Jubilee 2000 debt initiative and Make Poverty History; the widespread adoption and mainstreaming of digital communication techniques and social networks; steady growth in NGO fundraising revenues; the entire Millennium Development Goal story; and the establishment of a Westminster consensus on core elements of development policy. By many measures we have made amazing strides forward in recent years, but the public have largely been left behind. The result is that we operate within social and, by extension, political conditions that are precarious in the immediate term and incommensurate to the challenges of poverty and climate change in the medium and long term. This study looks at what can be learned from values (the guiding principles that individuals use to judge situations and determine their courses of action) and frames (the chunks of factual and procedural knowledge in the mind with which we understand situations, ideas and discourses in everyday life). Values and frames offer ways to look at the problem of public engagement with global poverty and to identify possible solutions. If we apply values and frames theory to the question of how to re-engage the public, we come up with some compelling insights into the impact of our existing practices and some striking solutions to the problems that these reveal. They may not be perfect solutions, and they bring with them significant challenges. But we believe they offer something valuable and timely: a fresh perspective. The persistent problem of public engagement suggests it is time for the development sector to transform its practices radically. Values and frames offer pathways to potential solutions that should be debated across the sector, and now
Pneumonia with bacterial and viral coinfection

Purpose of review We aim to review the epidemiology of pneumonia with bacterial and viral coinfection, the pathogenesis and clinical impact of coinfection along with the current state of treatment and outcomes. Recent findings Emphasis is given to the pathogenesis of bacterial and viral co-infection including specific highlighting on influenza, rhinovirus, respiratory syncytial virus and cytomegalovirus. Updates on the current state of diagnosis and management are included, as well as on areas where future research can be directed to improve patient clinical outcomes regarding viral and bacterial coinfection. Summary Bacterial and viral coinfection is increasingly recognized as an underlying etiology for community- and hospital-acquired infections. Coinfections may be a risk factor for ICU admission, severity of disease, and mortality. Clinicians must be aware of these coinfections for appropriate management and prognostication, as well as for the prevention of nosocomial spread of viral illness.
Lymphedema in Canada: a qualitative study to help develop a clinical, research, and education strategy.

OBJECTIVE The aim of this study was to gather data from Canadian stakeholders to help construct a national strategy and agenda for lymphedema management. METHODS The Canadian Lymphedema Framework, a collaboration of medical academics, lymphedema therapists, patient advocates, and others, used participatory action research and Open Space Technology to identify issues and build consensus at a national meeting of lymphedema stakeholders. Proceedings were videotaped and underwent content analysis. Existing Canadian documentation on lymphedema services was analyzed. Using those data sources, the Canadian Lymphedema Framework drafted a development strategy. RESULTS Of 320 invited stakeholders (patients, therapists, physicians, industry representatives, and health policymakers), 108 participated in a day-long videotaped meeting discussing strategies to improve the management of lymphedema and related disorders in Canada. Participants identified barriers, challenges, and issues related to the need to raise awareness about lymphedema with patients, physicians, and the public. Five priority areas for development were articulated: education, standards, research, reimbursement and access to treatment, and advocacy. The main barrier to development was identified as the lack of clear responsibility within the health care system for lymphedema care. CONCLUSIONS Data from stakeholders was obtained to solidly define priority areas for lymphedema development at a national level. The Canadian Lymphedema Framework has created a working plan, an advisory board, and working groups to implement the strategy.
Multidrug resistance in non-small-cell lung cancer.

Resistance to cytotoxic drugs is an important cause of treatment failure. The causes are complex and may be determined by a combination of the tumour characteristics, such as the proportion of resting cells, adequacy of blood supply, and specific cellular mechanisms, as in the multidrug resistance phenotype. In lung cancer four types of multidrug resistance have been defined on the basis of the cellular drug targets involved, i.e., classical multidrug resistance (MDR), non-P-glycoprotein MDR (also called MRP), atypical MDR (mediated through altered expression of topoisomerases II) and lung resistance-related protein. In lung cancer the role of the different forms of multidrug resistance is complex and only partially understood.
The Changing Nature of Real Exchange Rate Fluctuations. New Evidence for Inflation-Targeting Countries

We assess the role of real and nominal shocks on the real exchange rate (RER) dynamics for a set of small open economies. In doing so, we estimate a SVAR model for five inflation targeting countries: Australia, Canada, Chile, Israel and Norway. In sharp contrast with the existing empirical evidence, we find that in most countries demand shocks tend to explain a small proportion of RER volatility for the period 1986-2011. In that period nominal shocks are relatively more important in explaining RER fluctuations. When we perform a subsample analysis, however, we can reconcile the empirical findings in the literature with our results. In particular, we conclude that the relative importance of demand shocks has been declining substantially over time. In contrast, the relative importance of nominal shocks, and in particular exchange rate shocks, increased importantly in the last decade.
Examining the beliefs and practices of successful teachers in a high poverty school

The purpose of this qualitative study was to examine the beliefs and practices of successful teachers in a high poverty school. Specifically, this study examined the role of teacher beliefs and how these beliefs were enacted in the classroom. This multiple case study of three teachers took place in one middle school during a unit of study for each teacher and examined teacher experiences and instruction throughout the unit of study. Data collection included classroom observations, audio recorded interviews, teacher assignments and information from school, district and state websites. Data were analyzed using the constant comparative method (Strauss & Corbin, 1990). Through this analysis, three major themes surrounding teacher beliefs and practices emerged from the observation and interview data: (a) teacher beliefs enacted - this theme showed a connection between what participants said and what they did in their classrooms, particularly related to high expectations, student interests and needs, autonomy, social experiences, and cultural connections, (b) agency through resistance - teachers discussed in this study how they didn't feel they could be successful unless they pushed back against the standard curriculum by developing their own approach to teaching, which usually focused on culturally responsive teaching and building a community of learners and (c) support from colleagues and administration that impacted instructional decisions. These findings suggested that successful teachers in high poverty schools held and enacted beliefs that were centered on high expectations, social learning experiences and meeting the interests of students. As teachers acted on their beliefs, they also enacted agency in order to "push back" against the contextual constraints, primarily in regard to curriculum demands and assessment mandates, discussed in this study as "non-negotiables. " In order to meet these demands, while still enacting their beliefs, the successful teachers in this study had to consider what was indeed negotiable within the context of local, state, and national mandates. In determining how they could navigate these negotiables, these teachers were able to find a balance that allowed them to develop instruction to meet the unique needs of their students.
Quantitative Accuracy and Lesion Detectability of Low-Dose 18F-FDG PET for Lung Cancer Screening

Lung cancer remains responsible for more deaths worldwide than any other cancer, but recently there has been a significant shift in the clinical paradigm regarding the initial management of subjects at high risk for this disease. Low-dose CT has demonstrated significant improvements over planar x-ray screening for patient prognoses and is now performed in the United States. Specificity of this modality, however, is poor, and the additional information from PET has the potential to improve its accuracy. Routine screening requires consideration of the effective dose delivered to the patient, and this work investigates image quality of PET for low-dose conditions, in the context of lung lesion detectability. Reduced radiotracer doses were simulated by randomly discarding counts from clinical lung cancer scans acquired in list-mode. Bias and reproducibility of lesion activity values were relatively stable even at low total counts of around 5 million trues. Additionally, numeric observer models were developed and trained with the results of 2 physicians and 3 postdoctoral researchers with PET experience in a detection task; detection sensitivity of the observers was well correlated with lesion signal-to-noise ratio. The models were used prospectively to survey detectability of lung cancer lesions, and the findings suggested a lower limit around 10 million true counts for maximizing performance. Under the acquisition parameters used in this study, this translates to an effective patient dose of less than 0.4 mSv, potentially allowing a complete low-dose PET/CT lung screening scan to be obtained under 1 mSv.
Further attempts to transfer transplantation immunity by means of serum.

IT has been established beyond question that serum antibodies, demonstrable by haemagglutination (Gorer, 1947) or by nephelometric methods (Bollag, 1956), are formed in response to the grafting of homologous tissues; but there is strong evidence that, at least as far as serum haemagglutinins are concerned, these are not the operative agents of transplantation immunity (Mitchison and Dube, 1955; Kaliss, 1957). Attempts to transfer a state of heightened resistance against homografts of skin, using serum from specifically immunised mice, have so far been uniformly unsuccessful. Even regimens of daily or two-daily intraperitoneal inoculations of relatively large dosages of " immune " serum have failed to shorten the survival time of skin homografts in mice (Billingham, Brent and Medawar, 1954). The recent experiments of Voisin and Maurer (1956), while confirming that immunity may be transferred with cells, have given equivocal results with homologous " immune " serum. The purpose of this paper is to report on an extension of our earlier work in mice. Not only has an attempt been made to evoke a more vigorous and generalised immunological response from the serum donors, but special attention has been paid to the possibilities: (1) that the dosages of serum used in previous experiments might have been too high; (2) that it might be advantageous to begin treatment of the secondary hosts several days before transplanting to them their test-grafts; and (3) that the serum might be more effective if administered intraverously rather than intraperitoneally.
How Do Municipal Bonds Behave without Tax Exemption?

This article analyzes an extensive sample of tax-exempt and taxable municipal bonds to better understand how municipals behave without federal tax exemption. The authors find that taxable municipals are issued at higher yields in high state tax jurisdictions and that they are less likely to be issued in these areas and more likely to be issued in those that tax in-state issues. This finding suggests tax premium and market segmentation effects. As state tax treatment becomes more important, these effects may inhibit efficient portfolio diversification outcomes. The authors offer insight into how municipal portfolios and the municipal market behave in the absence of federal tax exemption.
Insertion mutagenesis of the lac repressor and its implications for structure-function analysis

We recently developed a simple technique for the generation of relatively large (31-codon) insertion mutations in cloned genes. To test whether the analysis of such mutations could provide insight into structure-function relationships in proteins, we examined a set of insertion mutants of the Escherichia coli lac repressor (LacI). Representatives of several LacI mutant classes were recovered, including mutants which exhibit fully active, inducer-insensitive, or weak dominant-negative phenotypes. The various properties of the recovered mutants agree with previous biophysical, biochemical, and genetic data for the protein. In particular, the results support the prior designation of mutationally tolerant spacer regions of LacI as well as proposed differences in dimerization interactions among regions of the protein core domain. These findings suggest that the analysis of 31-codon insertion mutations may provide a simple approach for characterizing structure-function relationships in proteins for which high-resolution structures are not available.
Serotonin transporter genotype and neuroanatomy in autism spectrum disorders

There is increasing evidence that people with autism spectrum disorders (ASDs) have abnormalities in the serotonergic system. For example, a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR long/short polymorphism) has been reported to confer risk for ASDs, and to affect cortical grey matter volume in young children. However, the persistence of this association later in development is unknown. Hence, we investigated whether variation in the 5HTTLPR long/short polymorphism modulates brain anatomy in older people with ASD. We related 5HTTLPR long/short polymorphism in 43 adolescents and adults with ASD to brain anatomy using structural magnetic resonance imaging and voxel-based morphometry. There were no significant associations between brain anatomy and genotype. When considered alongside evidence of a relationship between 5HTTLPR genotype and brain volume amongst children with autism, our findings raise the possibility that the relationship between 5HTTLPR polymorphism and brain anatomy in ASDs anatomy may differ as a function of age and/or ASD subdiagnosis.
Effects of reduced uterine blood flow on fetal cardiovascular, renal, and lung function.

Uterine blood flow (UBF) was reduced for 1 h by partially occluding the maternal aorta below the renal arteries in seven pregnant ewes (gestation age 126-134 days). Fetuses became hypoxic, acidemic, and hypercapnic. They developed hypertension (P less than 0.005) and a bradycardia (P less than 0.05). During restricted UBF, fetal hematocrit (Hct) rose (P less than 0.005) and blood volume fell in five of seven fetuses. After release of constriction, fetal Hct fell, and blood volume rose by 7.5 +/- 3.26% (P less than 0.05) relative to control. During reduced UBF, lung liquid and urine flow rates fell (P less than 0.025 and P less than 0.05, respectively). After the occluder was released, Na excretion (which did not fall significantly during reduced UBF) increased (P less than 0.05), and fractional reabsorption of Na fell (P less than 0.05). Changes in fetal blood volume (FBV) were directly related to changes in maternal lower body flow (r = 0.47, P = 0.01, n = 33), and changes in fetal Hct were inversely related to maternal flow (r = -0.635, P = 0.001). Fetal urinary Na excretion per kilogram body weight was directly related to FBV per kilogram (r = 0.44, P = 0.005, n = 40), whereas fractional reabsorption of Na was inversely related to FBV per kilogram body wt (r = 0.48, P less than 0.002, n = 39). It is concluded that reductions in UBF cause fetal hypoxemia and acidemia, which lead to changes in fetal cardiovascular function and in FBV. (ABSTRACT TRUNCATED AT 250 WORDS)