Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of a second HOXA2 nonsense mutation in a family with autosomal dominant non‐syndromic microtia and distinctive ear morphology

Microtia is a congenital defect affecting external ears, which appear smaller and sometimes malformed. Here we describe a five‐generation family with isolated bilateral microtia segregating as an autosomal dominant trait. Similar features have been previously observed in an autosomal dominant family with non‐syndromic microtia and hearing loss segregating with a HOXA2 nonsense variant. HOXA2 biallelic mutations were also described in an inbreed family with autosomal recessive microtia, hearing impairment and incomplete cleft palate. In our family, sequence analysis detected a heterozygous protein truncating nonsense variant [c.670G>T, p.(Glu224*)] segregating in all affected individuals and absent in public databases. This study confirms the role of HOXA2 gene in dominant isolated microtia and contribute to further define the dysmorphogenetic effect of this gene on ear development.
Deposition of Lipid, Protein, and Secretory Phospholipase A2 on Hydrophilic Contact Lenses

Purpose. Recent studies have shown that low tear phospholipid levels are associated with tear film instability in hydrophilic contact lens wearers. The concentration of secretory phospholipase A2 (sPLA2), the enzyme that hydrolyzes phospholipids, in tears is known to exceed the levels found in serum by four orders of magnitude. This study was performed to determine the levels of sPLA2 from the deposition on two different frequent-replacement contact lens materials. Methods. Polymacon and etafilcon A contact lenses worn for 2 weeks by 16 experienced contact lens wearers were used for the analysis. Total lipids were determined by the sulfo-phospho-vanillin reaction. Phospholipids in lipid extracts were estimated by phosphorus determination with ammonium molybdate through enzymatic digestion. Total protein was measured by bicinchoninic acid analysis. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine sPLA2 concentrations. Results. Total lipid deposition was found to be greater in the polymacon group (66.3 ± 16.3 &mgr;g/lens) than in the etafilcon A group, although phospholipids were not detected in either group. The etafilcon A group had greater deposition of protein (3.7 ± 0.7 mg/lens) than the polymacon group had. The etafilcon A group deposited statistically significantly more group IIa sPLA2 (1.1 ± 0.3 &mgr;g /lens) than the polymacon group (0.07 ± 0.04 &mgr;g/lens) did (P<0.001). Conclusions. There was a significant difference in the lipid and protein deposition profiles in the two lenses tested. A significant amount of sPLA2 in the deposition on contact lenses may play a role in tear film instability in hydrophilic contact lens wearers.
The relationship between physical activity and cognition in older Latinos.

OBJECTIVES The purpose of this study was to explore the relationship between minutes spent participating in light and moderate/vigorous-intensity physical activity (PA) and cognition in older Latinos, controlling for demographics, chronic health problems, and acculturation. METHOD A cross-sectional study design was used. Participants were self-identified Latinos, without disability, who had a score less than 14 on a 21-point Mini-Mental State Examination. Participants were recruited from predominantly Latino communities in Chicago at health fairs, senior centers, and community centers. PA was measured with an accelerometer, worn for 7 days. Episodic memory and executive function (inference control, inattention, and word fluency) were measured with validated cognitive tests. RESULTS Participants were 174 Latino men (n = 46) and women (n = 128) aged 50-84 years (M = 66 years). After adjusting for control variables (demographics, chronic health problems) and other cognitive measures, regression analyses revealed that minutes per day of light-intensity PA (r = -.51), moderate/vigorous PA (r = -.56), and counts per minute (r=-.62) were negatively associated with lower word fluency. DISCUSSION Findings suggest that the cognitive benefits of both light-intensity PA and moderate/vigorous PA may be domain-specific.
Inflation and Cost Push in Iran's Economy

There have been two broad theories of inflation, namely the demand-pull theory of inflation (that is nowadays mainly the monetary theory of inflation) and the cost-push theory of inflation. The mainstream macroeconomics views inflation as a monetary phenomenon in the long run. Iran has experienced double-digit rates of inflation for about four decades. Our main aim is an explanation for the long-run movements in the rate of inflation. We have used the raw data and the filtered data on the rate of inflation and the growth rate of the money supply to show that there is a long-run relationship. Also, we have used cointegration VAR method to show that there is a long-run relationship between the price level and the money supply but not between the price level and the cost-push factors. The empirical findings are not inconsistentwith the monetary theory of inflation in Iran.
From billionaires to the bottom billion: Who's making education policy for the poor in emerging economies?

Privatization of education is at a new and dangerous phase, particularly in emerging economies of Africa, Asia and Latin America, where multinational companies have their sights set on the profit potential of ‘education markets’ in these regions. The global market for education is estimated to reach $5 trillion, with much of this growth expected in Asia and Africa, with many of their countries having the highest proportion of school-age children in the world.1 While this chapter is based on research conducted in India,2 we find parallel trends of global corporate investment and profit-seeking ventures in the school sector in other developing and emerging economies. Our research focused on the city of Hyderabad in southern India that has the highest rates of school privatization in the country and is also home to technology giants such as Microsoft and Google. We made site visits to private schools and government schools in low-income neighbourhoods, interviewed principals and proprietors, consultants and start-up firms that are engaged in the design and delivery of services and
Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis.

BACKGROUND Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.
Voting Premium in Italy: An Analysis over a 30-Year Period

We investigate the different aspects affecting the control premium by carrying out an empirical analysis on the respective in the Italian stock market since 1987 employing the Voting Premium methodology. We demonstrate how the introduction of new regulations in this field in 2012 has contributed to a substantial premium reduction. The impact of the aforementioned regulations needs to be examined within the macroeconomic setting that has distinguished the period of reference, particularly the last decade, within which the decision to raise the tax rate on financial yields needs to be contextualized.
Routine Outcome Measurement in a Child and Adolescent Mental Health Service: An Evaluation of HoNOSCA

Objective: This paper evaluates a range of properties for a clinician-based instrument designed for routine use in a child and adolescent mental health service (CAMHS). Method: The Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) is a new outcome measure with great promise. Case vignettes were used to examine interrater reliability. HoNOSCA was implemented for routine outpatient use by multidisciplinary staff with a return rate of 84%. The 305 ratings obtained at assessment were analysed by age, gender and diagnosis. Asample of 145 paired ratings with a 3-month interval were examined for the measurement of change over time. Results: Interrater reliability of the total score indicates moderate reliability if absolute scores are used and good reliability if the total score is used for relative comparisons. Most scales have good to very good reliability. The scales discriminated between age and gender in the expected way. HoNOSCA correlated with clinicians’ views of change and was sensitive to change over a 3-month period. The total score seemed a proxy for severity. Conclusion: Routine outcome instruments must be explored in settings where they will be used and with realistic training. HoNOSCA appears to be of value in routine outcome measurement and although questions remain about reliability and validity, the results strongly support further investigation.
Passive respiratory mechanics measured during natural sleep in healthy term neonates and infants up to 8 weeks of life

The single occlusion technique (SOT) is a simple and noninvasive technique for measurement of passive respiratory mechanics in infants. Reference values based on measurements of a large population of healthy infants performed outside specialized research laboratories are lacking. The aim of this study was to present reference values for passive respiratory mechanics based on a large population of healthy term neonates and infants measured during natural sleep in routine care. As part of the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), the compliance (Crs) and resistance (Rrs) of the respiratory system were measured in 450 healthy unsedated neonates and infants with a mean age of 4.6 ± 1.3 weeks. Multivariable regression analysis, with gestational age, age at measurement, body size, sex, and ethnicity as possible predictors, was carried out to estimate prediction equations for mean Crs and Rrs values. Technically acceptable lung function measurements could be performed in 328 (73%) neonates and infants. Median Crs was 39.5 (range 14.8–79.1) ml/kPa and median Rrs was 7.4 (range 3.8–19.5) kPa/L/sec. The following regression equations for Crs and Rrs were obtained: ln Crs = 1.677 + 1.3 × 10−4 × birth weight (g) + 0.030 × birth length (cm) and ln Rrs = 2.496–3.1 × 10−6 × birth length3 (cm3) − 0.114 × sex. We provided reference values for passive respiratory mechanics using the SOT in a large population of healthy term neonates and infants measured during natural sleep. These data provide a frame of reference for assessing the normality of SOT measurements performed in routine care. Pediatr Pulmonol. 2006, 41:1058–1064. © 2006 Wiley‐Liss, Inc.
Toxoplasma evacuoles: a two‐step process of secretion and fusion forms the parasitophorous vacuole

Rapid discharge of secretory organelles called rhoptries is tightly coupled with host cell entry by the protozoan parasite Toxoplasma gondii. Rhoptry contents were deposited in clusters of vesicles within the host cell cytosol and within the parasitophorous vacuole. To examine the fate of these rhoptry‐derived secretory vesicles, we utilized cytochalasin D to prevent invasion, leading to accumulation of protein‐rich vesicles in the host cell cytosol. These vesicles lack an internal parasite and are hence termed evacuoles. Like the mature parasite‐containing vacuole, evacuoles became intimately associated with host cell mitochondria and endoplasmic reticulum, while remaining completely resistant to fusion with host cell endosomes and lysosomes. In contrast, evacuoles were recruited to pre‐existing, parasite‐containing vacuoles and were capable of fusing and delivering their contents to these compartments. Our findings indicate that a two‐step process involving direct rhoptry secretion into the host cell cytoplasm followed by incorporation into the vacuole generates the parasitophorous vacuole occupied by Toxoplasma. The characteristic properties of the mature vacuole are likely to be determined by this early delivery of rhoptry components.
Identification and characterisation of known and novel transcripts expressed during the final stages of human oocyte maturation

The final stages of oocyte maturation, from the germinal vesicle (GV) stage to metaphase II (MII) oocytes, are characterised by a series of dynamic events. These include germinal vesicle break down (GVBD), resumption of meiosis, and nuclear and cytoplasmic maturation to produce MII oocytes ready for fertilisation. To investigate the specific genes transcribed during these stages of oogenesis, we have prepared and analysed amplified cDNA representing the transcribed genes in a series of GV and MII oocytes. Differential display analysis disclosed that the overall gene expression profiles between different samples of GV oocytes are very similar, regardless of their source, while those between the MII oocytes are markedly variable. A comparison of expression profiles in oocytes and somatic (cumulus) cells identified several known genes preferentially‐expressed in oocytes (e.g., a zona pellucida gene), as well as five novel sequences. Two of the five novel sequences are homologous to retrotransposon sequences, long terminal repeat (LTR) and long interspersed nuclear element (LINE) 1, and two other sequences show partial homology to known ESTs and genomic sequences. The remaining sequence, which is identical to shorter ESTs isolated from germ cell tumor cDNA libraries, was extended towards its 5′ end by PCR, using the original cDNA preparation from which it was isolated as a template. Expression of the resultant 1.1‐kb transcript is restricted to the testis and ovary, and its expression correlates with cell pluripotency in that it is expressed in embryonal carcinoma cells, but not in their differentiated derivative cells. Mol. Reprod. Dev. 62: 13‐28, 2002. © 2002 Wiley‐Liss, Inc.
Genus and species-specific IgG and IgM antibodies for pulmonary tuberculosis.

OBJECTIVE To evaluate three different enzyme immunoassays for serological diagnosis of pulmonary tuberculosis and to compare their diagnostic accuracy in different combinations. DESIGN A non-interventional comparative study. PLACE AND DURATION OF STUDY The study was carried out at the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi between April and September 2001. SUBJECTS AND METHODS Sera from patients suffering from pulmonary tuberculosis (n=94) with sputum positive for acid fast bacilli (AFB) and sera from control group of healthy individuals (n=90) with sputum negative for AFB were tested by Pathozyme-Myco G EIA, Pathozyme-TB Complex Plus EIA and Pathozyme Myco M EIA kits for the genus-specific IgG and IgM, and the species-specific IgG antibodies against antigens of Mycobacterium tuberculosis. RESULTS The detection of IgG against genus-specific antigens by Pathozyme-Myco G had a sensitivity of 46% and a specificity of 93%, of IgG against species-specific antigens by Pathozyme-TB Complex Plus had a sensitivity of 64% and specificity of 97% and of IgM against genus-specific antigens by Pathozyme Myco M had a sensitivity of 67% and specificity of 98%. When the results of these immunoassays were evaluated in combination, their sensitivity improved. Combination of genus-specific IgM and species-specific IgG yielded best results with a sensitivity of 87% and specificity of 93%. CONCLUSION The sensitivity of serological diagnosis of tuberculosis is low, but it can be increased by utilizing a combination of several antigens.
Public procurement, innovation and policy : international perspectives

Foreword. - 1 Introduction. - 2 Public Procurement and Innovation: Theory and Practice. - 3 Australia. - 4 Brazil. - 5 China. - 6 Denmark. - 7 Estonia. - 8 Greece. - 9 Hong Kong. - 10 Korea. - 11 Sweden. - 12 United Kingdom. - 13 United States of America. - 14 Public Procurement, Innovation and Policy: Comparative Perspectives.
Principal components of electrocortical activity during self-evaluation indicate depressive symptom severity.

Negative self-evaluation is an important psychological characteristic of depression. In order to study the underlying neural mechanisms, we examined event-related potentials (ERPs) during a self-evaluation task in a community sample (N = 150) of adults reporting a range of depressive symptoms. Principal components analysis (PCA) was used to separate processes that overlap in the average ERP, and neural source analysis was applied to localize the ERP components, with a particular focus on the frontal networks that are thought to be critical to affective self-regulation in depression. Consistent with previous research, individuals reporting greater depression showed enhanced negativity over medial frontal regions as well as attenuation of the late positive potential over parietal regions. Examining loadings of frontal sources on the ERP components showed that activity in the right inferior frontal region may be particularly important for depressed individuals: activity in this region declined as symptoms became more severe. Characterizing brain mechanisms of self-evaluation on the timescale of cognitive events may provide insight into the neural mechanisms of self-regulation that are important in cognitive therapy, and that could be made more amenable to change through increasing neuroplasticity with targeted non-invasive neuromodulation.
Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study.

CONTEXT Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism, and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene (OPRM1). However, the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear. OBJECTIVES (1) To replicate and expand on the association between the A118G single nucleotide polymorphism(SNP) of the OPRM1 gene and alcohol sensitivity, (2) to examine the effects of naltrexone on alcohol sensitivity, and (3) to test the A118G SNP of the OPRM1 gene as a moderator of the effects of naltrexone on alcohol sensitivity. DESIGN A within-subject, double-blind, placebo-controlled laboratory trial of naltrexone. SETTING Participants were recruited from the community. PARTICIPANTS Non-treatment-seeking heavy drinkers were enrolled in the study. Prospective genotyping was conducted to oversample for the genetic variant of interest. Intervention After taking naltrexone (50 mg) or placebo, participants completed an intravenous alcohol challenge session in which they were assessed at baseline and at each of the 3 target breath alcohol concentrations: 0.02, 0.04, and 0.06 mg/L. MAIN OUTCOME MEASURES The Biphasic Alcohol Effects Scale, the Alcohol Urge Questionnaire, the Profile of Mood States, and the Alcohol Rating Scale were administered. RESULTS Individuals with at least 1 copy of the G allele reported lower alcohol craving and higher alcohol-induced "high" across rising breath alcohol concentrations. Naltrexone was found to blunt alcohol's effects on stimulation, positive mood, craving, and enjoyment. The effects of naltrexone on blunting alcohol-induced high were stronger among individuals with the G allele. CONCLUSION This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy.
Management of Multidirectional Instability of the Shoulder

&NA; Multidirectional shoulder instability is defined as symptomatic instability in two or more directions. Instability occurs when static and dynamic shoulder stabilizers become incompetent due to congenital or acquired means. Nonspecific activity‐related pain and decreased athletic performance are common presenting complaints. Clinical suspicion for instability is essential for timely diagnosis. Several examination techniques can be used to identify increased glenohumeral translation. It is critical to distinguish increased laxity from instability. Initial management begins with therapeutic rehabilitation. If surgical management is required, capsular plication has been used successfully. Advanced arthroscopic techniques offer several advantages over traditional open approaches and may have similar outcomes. The role of rotator interval capsular plication is controversial, but it may be used to augment capsular plication in patients with specific patterns of instability. Despite encouraging results, outcomes remain inferior to those associated with traumatic unidirectional instability.
Detection and Susceptibility Testing of Hypermutable Pseudomonas aeruginosa Strains with the Etest and Disk Diffusion

ABSTRACT Resistance development in Pseudomonas aeruginosa from chronically colonized cystic fibrosis (CF) patients has been linked to the presence of a high proportion of mismatch repair-deficient hypermutable strains. The detection of hypermutable strains by microbiology laboratories may be useful for establishing adequate antimicrobial therapies. In this work, we find that the Etest and disk diffusion can be used as simple methods for the detection and susceptibility testing of hypermutable P. aeruginosa isolates. Strain PAO1 and its hypermutable derivative strain PAOΔmutS were used to standardize the procedure, which was tested with 35 P. aeruginosa isolates from 21 CF patients. Mutation frequencies were estimated by standard methods, and 29% of the isolates were found to be hypermutable. MICs and inhibition zone diameters were determined for ceftazidime, imipenem, meropenem, ciprofloxacin, and tobramycin by using Etest strips and conventional disks, respectively. The presence (or absence) of resistant mutant subpopulations, as well as their relative numbers and the highest MICs for them (or smallest inhibition zone diameters), was recorded. The presence of resistant mutant subpopulations within the inhibition zones of three or more antibiotics clearly identified the strains as hypermutable (they were present in 10 of 10 hypermutable strains and 0 of 25 nonhypermutable strains) with both methods. Additionally, these methods allowed us to differentiate between dual effects of hypermutation in antibiotic resistance, namely, that (i) hypermutable isolates were substantially more resistant than nonhypermutable isolates and that (ii) the resistance of hypermutable isolates was dramatically increased by the presence of resistant mutant subpopulations. This differentiation may be relevant for the design of adequate treatments, since the second effect, in contrast to the first, may be overcome by antibiotic combinations.