Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic modifiers of the β‐haemoglobinopathies

Identification of the molecular basis of the β‐thalassaemias and sickle cell disease (SCD) has made it clear that patients with the same β‐globin genotypes can have very variable patterns of clinical expression. Extensive biochemical and pathophysiological studies over the last 50 years have derived two major modifiers – innate ability to produce fetal haemoglobin and co‐inheritance of α‐thalassaemia, subsequently validated by family and population studies. However, these two modifiers do not explain the full clinical spectrum. Genetic studies have been successful in identifying modifiers if the loci have a major clinical effect and if the genetic variants are common. It is possible that additional modifiers could be uncovered using genetic approaches but success will depend on large sample sizes of well‐characterised patients with well‐defined phenotypes. Since some of the complications, such as overt stroke in SCD, are relatively rare events, intermediate end‐points that contribute to the phenotype, such as Transcranial Doppler velocity (a major predictor of stroke in SCD), could be integrated within the genetic analysis. Integrating multiplex genetic testing with clinical and laboratory data to generate predictive models shows potential, but such genetic approaches also require large datasets.
Online Consultation and Governance Reform in Chinese Ministries and Provinces

This research examines the conditions under which Chinese central government ministries and provincial governments implement online consultation, a prominent instrument of governance reform in which officials provide interested parties with opportunities to offer feedback on proposed public policies. The research assembles original data regarding the online consultation practices of more than one hundred central government ministries and provincial governments. The analysis demonstrates that online consultation practices are more developed in provincial governments than central government ministries. Across organizational contexts, online consultation is more advanced in the disclosure of proposed policies than in the circulation of feedback submitted in response to draft laws and regulations. Finally, online consultation is primarily utilized by organizations with substantial resources, as well as organizations operating in environments not characterized by fundamental political sensitivities. These results are consistent with the expectation that although online consultation increases information disclosure and public participation in government decision making, such reforms are indicative not of the end of authoritarianism but rather the resilience of the Chinese Communist Party.
The association of aldose reductase gene (AKR1B1) polymorphisms with diabetic neuropathy in adolescents

Aims Variants in the aldose reductase gene (AKR1B1) have been implicated in the development of diabetic retinopathy and nephropathy, with the most convincing data identifying a (CA)n repeat microsatellite allele (Z−2), which has a functional role in gene expression. In this study the association between polymorphisms in the AKR1B1 gene and diabetic neuropathy was investigated.
Assessing the Reliability of Self‐reported Income Information in Informal Small Business Lending through a Bogus Pipeline Experiment

Coping with asymmetric information plays a major role in successful small business lending. Our purpose is to determine if small business applicants report their income information correctly when requesting a loan. We use a randomised controlled trial bogus pipeline experiment, established during a typical cash‐flow analysis of a bank for small businesses in the Philippines. The bogus pipeline approach is commonly applied in social science and aims to increase the rate of truth telling by informing participants that answers will be verified by a lie detector. The experimental data, which include 243 observations of credit clients that are mainly from the agricultural and food value chain, served to identify asymmetric information. Additionally, debtors’ repayment behaviour for approved loans was observed by the bank. Our results indicate that loan applicants of the treatment group report lower incomes, an effect which is most pronounced in lower income quantile. Our analyses also reveal higher loan delinquencies in the control group.
Is chronic widespread pain a predictor of all-cause morbidity? A 3 year prospective population based study in family practice.

OBJECTIVE To investigate whether chronic widespread pain predicts illness seen in general practice in a 3 year followup period. METHODS A postal questionnaire was conducted in an adult family practice population sample of 3968, and there were 2606 responders (66%). From the 2296 responders who consented to their record review, we identified 184 subjects with chronic widespread pain and assessed their outcome based on the first recorded morbidity within each of 15 categories during a 3 year followup period of computerized family practice records. Psychological distress at baseline was also measured using the Hospital Anxiety and Depression scale. RESULTS Of the survey responders, 2089 subjects (91%) completed the full 3 year followup period. Out of the 15 main morbidity categories examined, 11 were associated with pain status at baseline. The strongest associations between chronic widespread pain at baseline and subsequent morbidity, adjusted for age, sex, and social deprivation, were for musculoskeletal (MSK) disorders (rate ratio 4.36; 95% confidence interval 3.2-5.9), accidents (2.46; 95% CI 1.2-5.1), mental health disorders (2.24; 95% CI 1.5-3.3), dermatological disorders (2.16; 95% CI 1.6-2.9), and infections (1.96; 95% CI 1.3-2.9). Controlling for psychological distress reduced the strength of associations between chronic widespread pain and future morbidity, but 9 of the 11 were still statistically significant. In the 3 year followup period, an estimated 7.7% of all non-MSK and 12.6% of all MSK morbidity consultations were related to chronic widespread pain as reported at baseline. CONCLUSION People who report chronic widespread pain subsequently consult more frequently about non-MSK and MSK problems than people with no pain, and this is not explained by psychological distress. The overall impact on healthcare use is substantial. Our study provides more evidence for overlap and links between morbidities that may be part of a larger pathological or somatization syndrome.
Cardiovascular effects of moderate normovolaemic haemodilution during enflurane-nitrous oxide anaesthesia in man.

The cardiovascular effects of mild normovolaemic haemodilution during enflurane-nitrous oxide anaesthesia were studied in 20 patients with normal cardiac function before, during and after total hip replacement. After induction of anaesthesia, patients were randomly allocated to one control group (C), or one haemodiluted group (H) where Hct was decreased to 30% by replacement of blood volume by an identical volume of hydroxyethyl starch 200/05. Each patient was monitored with a pulmonary artery catheter allowing the measurement of right ventricular ejection fraction. During haemodilution, stroke index and right ventricular end-diastolic volume index increased from 33.1 +/- 7.9 to 39.3 +/- 7.1 ml.M-2 and from 73.8 +/- 20.3 to 94.9 +/- 18.5 ml.M-2 respectively (mean +/- s.d., both P < 0.05). However, heart rate decreased so that cardiac index did not change. O2 delivery decreased significantly (from 389 +/- 70 to 311 +/- 63 ml.min-1.m-2; P < 0.05), but was not different to the control group. O2 consumption was maintained by an increase in O2 extraction. During the surgical procedure, cardiac index was higher in the haemodiluted group than in the control group, so that O2 delivery was similar in the two groups. O2 consumption tended to be greater in the haemodiluted group. In patients with normal cardiac function, enflurane-nitrous oxide anesthesia could alter the normal physiologic response to mild normovolaemic haemodilution.
Understanding the Process of Prioritizing Fruit and Vegetable Purchases in Families With Low Incomes: “A Peach May Not Fill You Up as Much as Hamburger”

Fruits and vegetables (F&V) are an important component of a healthy diet, but few children are meeting the recommended number of servings. Children from families with limited resources may be least likely to meet the recommendation. This study was designed to understand the strategies and priorities of families with low income related to purchasing F&V. We conducted qualitative, in-depth telephone interviews with low-income parents of elementary school–aged children as part of a random sample of parents participating in a telephone survey who agreed to be contacted for an in-depth interview. Interview transcripts were coded based on predetermined codes that were informed by the research questions. F&V were not considered staples by parents and cost was one of the main concerns. Parents equated F&V with fresh F&V. Interventions encouraging F&V purchasing by families with low income need to find new ways to address the issue of cost, including advocating for F&V in all forms (fresh, frozen, canned, and dried).
Glycogen synthase kinase 3β missplicing contributes to leukemia stem cell generation

Recent evidence suggests that a rare population of self-renewing cancer stem cells (CSC) is responsible for cancer progression and therapeutic resistance. Chronic myeloid leukemia (CML) represents an important paradigm for understanding the genetic and epigenetic events involved in CSC production. CML progresses from a chronic phase (CP) in hematopoietic stem cells (HSC) that harbor the BCR-ABL translocation, to blast crisis (BC), characterized by aberrant activation of β-catenin within granulocyte-macrophage progenitors (GMP). A major barrier to predicting and inhibiting blast crisis transformation has been the identification of mechanisms driving β-catenin activation. Here we show that BC CML myeloid progenitors, in particular GMP, serially transplant leukemia in immunocompromised mice and thus are enriched for leukemia stem cells (LSC). Notably, cDNA sequencing of Wnt/β-catenin pathway regulatory genes, including adenomatous polyposis coli, GSK3β, axin 1, β-catenin, lymphoid enhancer factor-1, cyclin D1, and c-myc, revealed a novel in-frame splice deletion of the GSK3β kinase domain in the GMP of BC samples that was not detectable by sequencing in blasts or normal progenitors. Moreover, BC CML progenitors with misspliced GSK3β have enhanced β-catenin expression as well as serial engraftment potential while reintroduction of full-length GSK3β reduces both in vitro replating and leukemic engraftment. We propose that CP CML is initiated by BCR-ABL expression in an HSC clone but that progression to BC may include missplicing of GSK3β in GMP LSC, enabling unphosphorylated β-catenin to participate in LSC self-renewal. Missplicing of GSK3β represents a unique mechanism for the emergence of BC CML LSC and might provide a novel diagnostic and therapeutic target.
Gender and cancer support group participation.

PURPOSE Although support groups are offered to many patients who have received a diagnosis of cancer, a majority of patients choose not to participate. This article reports the results of a study comparing the behavior of men diagnosed with prostate cancer and women diagnosed with breast cancer in their responses to invitations to participate in support groups. DESCRIPTION OF STUDY One hundred thirty women with breast cancer and 87 men with prostate cancer completed a structured telephone interview. The interview included questions about the patients' choices about support group participation. RESULTS Interview findings showed that men are less likely to join a support group, but those men who do join attend meetings for about 1 year, as do the women who join. Men and women cite essentially the same reasons for participation: to learn more about their diagnosis, to share their, concerns to compare their physical and emotional progress with other individuals. CLINICAL IMPLICATIONS These results indicate the need for further exploration of effective interventions for men and women who have been diagnosed with prostate and breast cancer, respectively, in an effort to offer support for the difficult psychological and emotional issues associated with their diagnoses. Although more women than men join support groups, the majority of both populations (67% for women, 87% for men) do not attend any support group meetings. Innovative approaches are needed to encourage participation in existing support groups or to design alternative interventions.
Akt regulates TPP1 homodimerization and telomere protection

Telomeres are specialized structures at the ends of eukaryotic chromosomes that are important for maintaining genome stability and integrity. Telomere dysfunction has been linked to aging and cancer development. In mammalian cells, extensive studies have been carried out to illustrate how core telomeric proteins assemble on telomeres to recruit the telomerase and additional factors for telomere maintenance and protection. In comparison, how changes in growth signaling pathways impact telomeres and telomere‐binding proteins remains largely unexplored. The phosphatidylinositol 3‐kinase (PI3‐K)/Akt (also known as PKB) pathway, one of the best characterized growth signaling cascades, regulates a variety of cellular function including cell proliferation, survival, metabolism, and DNA repair, and dysregulation of PI3‐K/Akt signaling has been linked to aging and diseases such as cancer and diabetes. In this study, we provide evidence that the Akt signaling pathway plays an important role in telomere protection. Akt inhibition either by chemical inhibitors or small interfering RNAs induced telomere dysfunction. Furthermore, we found that TPP1 could homodimerize through its OB‐fold, a process that was dependent on the Akt kinase. Telomere damage and reduced TPP1 dimerization as a result of Akt inhibition was also accompanied by diminished recruitment of TPP1 and POT1 to the telomeres. Our findings highlight a previously unknown link between Akt signaling and telomere protection.
Heavy metals in raw cow and ewe milk from north-east Iran

The presence of toxic metals in milk may create significant health problems for the population. In this study, 1440 raw cow and ewe milk samples from 18 townships in north-east Iran were analysed in four different seasons. Lead, cadmium and mercury levels were determined using atomic absorption spectrophotometry. Mean concentration of lead, cadmium and mercury in cow milk samples was 12.9 ± 6.0, 0.3 ± 0.3 and 3.1 ± 0.3 ng g−1, respectively, and in ewe milk samples, these mean values were 14.9 ± 7.8, 1.6 ± 1.2 and 3.1 ± 0.3 ng g−1, respectively. Statistical analyses showed that lead and cadmium concentrations in ewe milk were significantly higher than in cow milk. Concentrations of these metals in ewe milk varied significantly with different seasons. As the concentrations did not exceed the safety limits, they could not pose a serious danger to public health.
Environmental Policy When Market Structure and Plant Locations are Endo-Genous

A two-region, two-firm model is developed in which firms choose the number and the regional locations of their plants. Both firms pollute and, in this context, market structure is endogenous to environmental policy. There are increasing returns at the plant level, imperfect competition between the "home" and the "foreign" firm, and transport costs between the two markets. These features imply that at critical levels of environmental policy variables, small policy changes cause large discrete jumps in a region's pollution and welfare as a firm closes or opens a plant, or shifts production for the foreign region from/to the home-region plant to/from a foreign branch plant. The implications for optimal environmental policy differ significantly from those suggested by traditional Pigouvian marginal analysis.
Comparison of Three Techniques for Repair of Involutional Lower Lid Entropion: A Three-Year Follow-Up Study

Objective: The aim of this study was to quantify the efficacy of three different surgical techniques for entropion repair in a 3-year follow-up study: (1) the Fox procedure, (2) everting sutures and (3) a modified technique of lower lid retractor plication. Methods: We included in our study 32 eyelids of 32 consecutive patients with involutional lower lid entropion; 10 lids underwent the Fox procedure, 13 the everting sutures and 9 the modified retractor plication. We evaluated the pre- and postoperative horizontal lid laxity (HLL), the pre- and postoperative lower lid excursion (LLE) and the number of recurrences in each patient group. Statistical analysis was performed with the non-parametric Mann-Whitney test and the exact Fisher’s test where appropriate. Results: Only the modified retractor plication technique showed statistically significant differences in HLL and LLE (p < 0.05). In the group treated with this technique, there was a lower incidence of entropion recurrence (p < 0.05). The everting suture technique showed a statistically significant improvement of the LLE only (p < 0.05). The Fox procedure did not show any statistically significant improvement of the studied parameters. Conclusions: The modified retractor plication technique gave the best results in terms of improvement of HLL and LLE and a lower incidence of entropion recurrence compared to the two other techniques studied.
Varieties of Object Constancy

Three experiments are described in which two pictures of isolated man-made objects were presented in succession. The subjects’ task was to decide, as rapidly as possible, whether the two pictured objects had the same name. With a stimulus-onset asynchrony (SOA) of above 200 msec two types of facilitation were observed: (1) the response latency was reduced if the pictures showed the same object, even though seen from different viewpoints (object benefit); (2) decision time was reduced further if the pictures showed the same object from the same angle of view (viewpoint benefit). These facilitation effects were not affected by projecting the pictures to different retinal locations. Significant benefits of both types were also obtained when the projected images differed in size. However, in these circumstances there was a small but significant performance decrement in matching two similar views of a single object, but not if the views were different. Conversely, the object benefit, but not the viewpoint benefit, was reduced when the SOA was only 100 msec. The data suggest the existence of (at least) two different visual codes, one non-retinotopic but viewer-centred, the other object-centred.
Detection of Modified Tyrosines as an Inflammation Marker in a Photo‐aged Skin Model

Reactive nitrogen species, produced during the process of inflammation induced by various factors including UV radiation, modify amino acids in crucial proteins. It is assumed that skin tissue is more likely to be modified, as it is located at the outer layer of a body that is exposed to UV radiation on a daily basis. To investigate the influence of the modified tyrosine on UV‐exposed skin, we detected the nitrotyrosine or halogenated tyrosine and dityrosine in photo‐aged model mice. The back skin of mice was exposed to a dose of 10 J cm−2 day−1 every day for 15 weeks. Samples exhibiting typical symptoms of photo aging were provided to the immunofluorescence study. The quantification of modified proteins was accomplished through a chemical analytical method known as HPLC‐tandem mass spectrometry. Analysis of the irradiated skin samples showed that all modified tyrosine except nitrotyrosine demonstrated statistically significant increases. The molecular weights of major modified proteins, confirmed as 25–50 kDa, were measured using Western blot analysis with an anti‐nitrotyrosine antibody. Furthermore, the immunofluorescence study verified that the localization of myeloperoxidase conformed to that of nitrotyrosine. This result suggests that the modified tyrosine was produced during the process of inflammation by UV irradiation. In this study, we used a low dose of UV irradiation to which we are exposed in daily life. Our results suggest that UV exposure in daily life may induce the production of modified tyrosines and skin aging.
Determinants of folic acid knowledge and use among antenatal women.

BACKGROUND Although recommendations on folic acid use were issued by health authorities in a number of countries in the early 1990s, uptake of peri-conceptional folic acid is still disappointingly low. Regardless of food fortification policies, folic acid promotion will probably be required in most countries to optimize folate levels among women of child-bearing age. The aim of this study was to examine folic acid knowledge and use, and their determinants among antenatal women in the east of Ireland in 1997. METHODS Three hundred antenatal women attending their initial booking appointment in three Dublin maternity hospitals were surveyed. An interviewer-administered questionnaire was used with questions on folic acid knowledge and use, and demographic and obstetric questions. A univariate analysis of data was undertaken followed by a multivariate analysis using logistic regression to determine factors predicting knowledge and use of folic acid. RESULTS Seventy-six per cent of respondents had heard of folic acid, 16 per cent had taken it before pregnancy and 51 per cent during pregnancy. Women who had planned their pregnancy, were married and were relatively affluent were significantly more likely to have heard of folic acid, to know that it could prevent neural tube defects and to have taken it peri-conceptionally. Less affluent women tended to use their general practitioner (GP) more as a source of information and advice than those who were better off. In multivariate analysis, marriage and planned pregnancy were important predictors of folic acid knowledge whereas planned pregnancy advice given before pregnancy and relative affluence were predictive of peri-conceptional use. CONCLUSIONS Many women know of folic acid but do not take it peri-conceptionally. Women may associate folic acid with pregnancy and less with pre-pregnancy. Greater emphasis on peri-conceptional use should improve folic acid uptake. Focusing on less affluent women for folic acid promotion by GPs and other primary care professionals is also important.
Determinants of adherence to lifestyle intervention in adults with obesity: a systematic review

Lifestyle intervention programmes are efficacious in the management of obesity but often report poor attendance and adherence rates that hinder treatment effectiveness and health outcomes. The aim of this systematic review is to identify (i) barriers to behaviour change and (ii) predictors of adherence to lifestyle intervention programmes in adults with obesity. Studies were identified by systematically reviewing the literature within Medline, PsycINFO, CINAHL, SPORTDiscus and Web of Science from inception to August 2016. Barriers to behaviour change include poor motivation; environmental, societal and social pressures; lack of time; health and physical limitations; negative thoughts/moods; socioeconomic constraints; gaps in knowledge/awareness; and lack of enjoyment of exercise. The most prominent predictors of adherence include early weight loss success, lower baseline body mass index (BMI), better baseline mood, being male and older age. The findings within this review provide novel insight to clinicians working in obesity and have important implications for lifestyle intervention programme design. Barriers to behaviour change need to be addressed early in treatment, with lifestyle intervention individualized accordingly. Predictors of adherence should also be taken into careful consideration, with negative moods and unrealistic weight loss expectations discussed at the outset. If adherence is improved, treatment effectiveness, health outcomes and the ultimate burden of chronic diseases could also be improved.