Miracle-dz/UniFAR-FTUs huggingface dataset:
Simeprevir plus sofosbuvir for eight or 12 weeks in treatment‐naïve and treatment‐experienced hepatitis C virus genotype 4 patients with or without cirrhosis

The OSIRIS study investigated efficacy and safety of simeprevir plus sofosbuvir for eight or 12 weeks in hepatitis C virus (HCV) genotype 4‐infected patients with METAVIR F0‐F4 fibrosis. Sixty‐three patients (33 treatment‐naïve and 30 peg‐interferon/ribavirin (Peg‐IFN/RBV)‐experienced) enrolled in a partly randomized, open‐label, multicentre, phase IIa study. Patients with F0‐F3 fibrosis were randomized (1:1) into two groups (A1 and A2), stratified according to treatment experience and METAVIR score, to receive either eight weeks (Group A1, n=20) or 12 weeks (Group A2, n=20) of treatment. Patients with compensated cirrhosis (METAVIR F4) received 12 weeks of treatment (Group B, n=23). Treatment comprised simeprevir 150 mg and sofosbuvir 400 mg daily. The primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12). Safety and tolerability were assessed throughout. Overall, 92% (95% CI: 82‐97) of patients achieved SVR12; 75% (15/20) in Group A1 and 100% in groups A2 and B. Patients who did not achieve SVR12 (n=5) experienced viral relapse during the first 32 days following treatment and were all prior Peg‐IFN/RBV null responders. The most commonly reported treatment‐emergent adverse events (TEAEs) were asymptomatic lipase increase (14%), pruritus (14%), headache (13%) and hyperbilirubinaemia (11%). No patients discontinued due to TEAEs. In conclusion, simeprevir plus sofosbuvir for 12 weeks achieved a 100% SVR rate in HCV genotype 4‐infected patients with or without compensated cirrhosis (ClinicalTrials.gov: NCT02278419). The AE and laboratory profile were favourable and consistent with previous data for simeprevir plus sofosbuvir in eight‐ and 12‐week regimens.
Structural covariance in the cortex of very preterm adolescents: A voxel‐based morphometry study

On the basis of findings in normative samples that different cortical brain regions covary in gray matter volume, most likely as a result of mutually trophic influences during cortical development, we aimed to study whether patterns of covariation in regional gray matter, i.e., structural covariance, differed between adolescents who were born very preterm and full‐term controls. Optimized voxel‐based morphometry was used to study structural magnetic resonance imaging scans from 218 very preterm adolescents (gestational age <33 weeks) and 127 controls at 14–15 years of age. Local gray matter volumes were obtained for 18 regions of interest involved in sensorimotor and higher‐order cognitive functions. These were then used to predict local volumes in the remaining areas of the cortex, with total gray matter volume, age and gender used as confounding variables. Very preterm adolescents compared with controls demonstrated differential (i.e., both increased and decreased) structural covariance between medial, frontal and cingulate gyri, caudate nucleus, thalamus, primary visual cortex, cerebellum and several other cortical and subcortical regions of the cortex. These findings support previous research indicating that preterm birth is associated with altered cortical development, and suggest that developmental changes in one brain region may result in a cascade of alterations in multiple regions. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Tooth‐On‐Tooth Interlocking Occlusion Suggests Macrophagy in the Mesozoic Marine Crocodylomorph Dakosaurus

Metriorhynchidae was a peculiar but long‐lived group of marine Mesozoic crocodylomorphs adapted to a pelagic lifestyle. Recent discoveries show that metriorhynchids evolved a wide range of craniodental morphotypes and inferred feeding strategies. One genus, Dakosaurus, is arguably the most aberrant marine crocodylomorph due to its large, robust, ziphodont teeth; very low tooth count; and brevirostrine/oreinirostral snout. We here report an additional unusual feature of Dakosaurus that is unique among marine crocodylomorphs: tightly fitting tooth‐to‐tooth occlusion, whose inference is supported by reception pits along the upper and lower tooth rows, indicative of vertically orientated crowns that were in close contact during occlusion, and three distinct types of dental wear. These include irregular spalled surfaces near the apex (probably caused by tooth‐food contact), semi‐circular wear near the base, and elongate surfaces extending along the mesial and distal margins of the teeth, obliterating the carinae (including the denticles). Scanning electron micrographs show that these latter surfaces are marked by parallel apicobasal striations, which in extant mammals reflect tooth–tooth contact. As such, we interpret the carinal wear facets in Dakosaurus as being formed by repeated tooth–tooth contact between the mesial and distal margins of the teeth of the upper and lower jaw. We posit that this increased the available shearing surface on their high crowns. Together, these wear patterns suggest that occlusion in Dakosaurus was specialized for cutting large and abrasive prey items into portions small enough to swallow, making it a prime example of an aquatic reptile with macrophagous feeding habits. Anat Rec, 2012. © 2012 Wiley‐Periodicals, Inc.
Genetic Dissection of Lupus Pathogenesis: Sle3/5 Impacts IgH CDR3 Sequences, Somatic Mutations, and Receptor Editing1

Sle3/5 is a lupus susceptibility locus identified on mouse chromosome 7 of the New Zealand Black/New Zealand White (NZB/NZW)-derived NZM2410 strain. Based on previous observations, this locus appears to contribute to lupus pathogenesis through its impact on diversification of immune responses. To understand how Sle3/5 affects somatic diversification of humoral responses, we analyzed IgH rearrangements preferentially encoding hapten-reactive IgG1 repertoires after immunization and assessed peripheral IgH VDJ recombination activities in C57BL/6 (B6) mice congenic for Sle3/5 (B6.Sle3/5). In addition to altered somatic VH mutation profiles, sequences from B6.Sle3/5 mice exhibited atypical IgH CDR3 structures characteristic of autoreactive B cells and consistent with peripheral B cells bearing putatively edited receptors. Significant expression of Rag genes and circular VHD gene excision products were detected in splenic mature B cells of B6.Sle3/5 but not B6 mice, showing that peripheral IgH rearrangements occurred beyond allelic exclusion. Taken together, on the nonautoimmune background, Sle3/5 affected VHDJH junctional diversity and VH mutational diversity and led to recombinational activation of allelically excluded IgH genes in the periphery. Such impact on somatic IgH diversification may contribute to the development of autoreactive B cell repertoires. This is the first report to present evidence for significant association of a lupus susceptibility locus, which has been mapped to a chromosomal region in which no Ig genes have been identified, with somatic IgH sequence diversity and peripheral H chain receptor editing or revision without relying upon Ig transgene strategies.
Race, Sex, and Discrimination in School Settings: A Multilevel Analysis of Associations With Delinquency.

BACKGROUND Adolescence is a critical phase of development and experimentation with delinquent behaviors. There is a growing body of literature exploring individual and structural impacts of discrimination on health outcomes and delinquent behaviors. However, there is limited research assessing how school diversity and discrimination impact students' delinquent behaviors. In response, the purpose of this study was to assess if individual- and school-level indicators of discrimination and diversity were associated with student delinquent behaviors among African American and White students. METHODS We analyzed Wave I (1994-1995) data from the National Longitudinal Study of Adolescent Health. Our analysis was limited to 8947 African American and White students (73% White, 48% male, and 88% parent ≥ high school education). We used multilevel zero-inflated negative binomial regression to test the association of individual- and school characteristics and discrimination with the number of self-reported delinquent behaviors. RESULTS Race, sex, perceived peer inclusion, and teacher discrimination were predictors of students' delinquent behaviors. The average school perceived peer inclusion and percentage of African Americans in teaching roles were associated with delinquent behaviors. CONCLUSIONS Findings from this study highlight the potential for intervention at the interpersonal and school levels to reduce delinquency among African American and White students.
Modulation of Glucocorticoid Receptor Gene Expression by Antidepressant Drugs

Through expression of a glucocorticoid receptor (GR) antisense RNA in brain, we have produced transgenic mice with an hyperactive hypothalamic-pituitary-adrenocortical (HPA) system similar to that seen in depressed patients. This model supports the hypothesis that disturbed corticosteroid receptor regulation could be the primary factor responsible for both the CRH/AVP hyperdrive that leads to increased activity of the HPA system, and the premature escape from the cortisol suppressant action of dexamethasone seen in affective disorders. Although normalisation of the hyperactive HPA system occurs during successful antidepressant therapy of depressive illness, these improvements do not correlate with changes in monoaminergic neurotransmitter systems, suggesting that unknown mechanisms of action may be operative. Work from my laboratory was the first to show that different types of antidepressants increased glucocorticoid receptor (GR) mRNA. We found increased GR mRNA levels irrespective of the preferential inhibitory action of antidepressant on the monoamine neurotransmitter re-uptake and showed increased GR gene transcription in antidepressant-treated mouse fibroblast cells that do not possess monoamine re-uptake mechanisms. We measured changes in glucocorticoid response in cells transfected with a glucocorticoid-sensitive reporter plasmid (MMTV-CAT) and observed increased glucocorticoid-stimulated CAT activity when the cells were treated with antidepressant. A different chimaeric gene construct consisting of a fragment of the GR gene promoter region fused to the CAT gene allowed more direct measurement of antidepressant action and increased CAT activity was also seen when cells transfected with this construct were treated with antidepressant. Finally, GR mRNA concentration and glucocorticoid binding activity were increased in brain tissues of animals chronically treated with antidepressant. The time course of antidepressant actions on corticosteroid receptors coincides with their long-term actions on HPA system activity and follows closely that of clinical improvement of depression. This suggests that antidepressant-induced changes in brain corticosteroid receptors may underlie the observed simultaneous decrease in circulating ACTH and corticosterone levels and the decreased adrenal size. Some of these effects may be mediated through CRH since, in antidepressant-treated transgenic mice hypothalamic CRH mRNA levels were decreased. From this work we have formulated the hypothesis that a primary action of antidepressants could be the stimulation of corticosteroid receptor gene expression that renders the HPA system more susceptible to feedback inhibition by cortisol. The resultant decrease in HPA system activity could induce secondary changes in glucocorticoid-sensitive gene expression and lead to redressment of neurotransmitter imbalance. This work opens up a completely new insight into antidepressant drug action and suggests a line of approach to the development of new drugs by focusing on this action.
Performance Enhancement in Uniaxially Strained Germanium–Tin FinTFET: Fin Direction Dependence

We investigate the impact of uniaxial tensile stress on the performance of germanium–tin (GeSn) fin tunneling field-effect transistor (FinTFET) with fin rotating within (001) plane by numerical simulation. The uniaxial tensile stress with a magnitude of 1 GPa is always along the fin direction. Nonlocal empirical pseudopotential method and k <inline-formula> <tex-math notation="LaTeX">$\cdot $ </tex-math></inline-formula> p method were utilized to calculate the energy band structure of GeSn. Dynamic nonlocal band-to-band tunneling (BTBT) algorithm was used to analyze the electrical characteristics of the strained GeSn FinTFETs with point and line tunneling modes. The substantial improvement of BTBT generation rate <inline-formula> <tex-math notation="LaTeX">${G}_{\text {BTBT}}$ </tex-math></inline-formula> and on-state current <inline-formula> <tex-math notation="LaTeX">${I}_{ \mathrm{\scriptscriptstyle ON}}$ </tex-math></inline-formula> achieved in tensile-strained FinTFETs compared to the relaxed devices is attributed to the reduced direct bandgap <inline-formula> <tex-math notation="LaTeX">${E}_{G}$ </tex-math></inline-formula> in strained GeSn. The device performance enhancement induced by the stress demonstrates the obvious dependence on the fin direction and tunneling mode. Under 1 GPa uniaxial tensile stress, GeSn point-FinTFETs with <inline-formula> <tex-math notation="LaTeX">$\langle 100\rangle $ </tex-math></inline-formula> fin directions demonstrate an 11.7% <inline-formula> <tex-math notation="LaTeX">${I}_{ \mathrm{\scriptscriptstyle ON}}$ </tex-math></inline-formula> enhancement as compared with the relaxed devices. For the strained GeSn line-FinTFETs, the devices with <inline-formula> <tex-math notation="LaTeX">$\langle 110\rangle $ </tex-math></inline-formula> fin directions obtain a 96.7% <inline-formula> <tex-math notation="LaTeX">${I}_{ \mathrm{\scriptscriptstyle ON}}$ </tex-math></inline-formula> improvement, in comparison with the relaxed devices at <inline-formula> <tex-math notation="LaTeX">${V}_{\text {DD}}$ </tex-math></inline-formula> of −0.3 V.
AIDS as social construction: text mining of AIDS-related information in the Italian press

ABSTRACT Given the relevance of AIDS as a public health problem in the Italian context and of the role of mass media in the social construction of the phenomenon, the aim of the present study is twofold: (1) to explore the main AIDS-related themes in the Italian popular press; (2) to analyse the temporal trends of AIDS representations over the last decades. For the research, we decided to consult Italian newspaper articles produced between 1985 and 1990 and between 2005 and 2010 using the archives of the main two national newspapers (La Repubblica and Corriere della Sera), resulting in an overall sample of 446 newspaper articles. A computer-aided content analysis allowed the detection of five different thematic domains (clusters), respectively focused on: Medical care (7.47%), Family support (37.03%), Science and religion debate (27%), Social exclusion (17.6%) and Healthcare policies (10.9%). These thematic domains are conceived along two main latent dimensions (factors) which explain 72.47% of the data variance which respectively deal with: (1) Attitudes towards people with AIDS (care versus avoidance) and (2) Social mandate on AIDS (powerlessness versus control). The study results also reveal the potential evolution of representations of people with AIDS over time: from stigmatised subjects who represent a risk for the entire society within a climate of social control to people progressively symbolised as frail subjects that need to be taken care of.
Parkinson's Disease and Cognitive-Motor Dual-Task: Is Motor Prioritization Possible in the Early Stages of the Disease?

ABSTRACT The authors aimed to compare the postural phase of gait initiation under single-task (gait initiation) and dual-task (gait initiation plus Stroop test) conditions in healthy subjects and in subjects with Parkinson's disease (PD) in the early stages (Hoehn and Yahr scale < 3). The postural phase of gait initiation was assessed through the centre of pressure in single and dual task in 10 healthy subjects and 9 with PD. The analysis indicated that in the early stages of PD, an additional cognitive task did not affect the displacement of the gait initiation. No significant effects occurred between the groups and within-subjects (p > .05). Also, no interaction was found between the groups and the conditions (single- and dual-task). Differences were found in the duration of the mediolateral postural phase (p = .003), which was higher in PD subjects than in healthy subjects. The findings suggest that subjects in the early stages of PD prioritize gait initiation, as their motor performance was similar to that of healthy subjects.
Impulse Oscillometry vs. Body Plethysmography in Assessing Respiratory Resistance in Children

In 334 children aged 5–18 years, we compared the results of plethysmographic measurements of airway resistance (Raw) with oscillometric (impulse oscillometry; IOS) assessment of respiratory properties of the respiratory system (resistance (R) at 5, 20, and 35 Hz). All three resistances correlated significantly with plethysmographic Raw, and the strongest correlation was seen for R5 (r = 0.64). R5, R20, and R35 were significantly greater than Raw in the whole group. In the group of children with obstruction (FEV1%FVC below lower limit of normal), R5 was still greater than Raw, while R20 and R35 were not. The Bland‐Altman analysis comparing plethysmographic measurements with oscillometric R5 revealed a significant difference between Raw and R5 in the whole group, which disappeared in the group of obstructed patients. Oscillometric assessment of resistive properties of the respiratory system of the lung requires less patient cooperation than does plethysmography. As the results of measurements using oscillometric R5 are similar to those obtained by plethysmography, IOS may be useful in diagnosing children with obstructive respiratory diseases. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
An interdomain boundary in RAG1 facilitates cooperative binding to RAG2 in formation of the V(D)J recombinase complex

V(D)J recombination assembles functional antigen receptor genes during lymphocyte development. Formation of the recombination complex containing the recombination activating proteins, RAG1 and RAG2, is essential for the site‐specific DNA cleavage steps in V(D)J recombination. However, little is known concerning how complex formation leads to a catalytically‐active complex. Here, we combined limited proteolysis and mass spectrometry methods to identify regions of RAG1 that are sequestered upon association with RAG2. These results show that RAG2 bridges an interdomain boundary in the catalytic region of RAG1. In a second approach, mutation of RAG1 residues within the interdomain boundary were tested for disruption of RAG1:RAG2 complex formation using fluorescence‐based pull down assays. The core RAG1 mutants demonstrated varying effects on complex formation with RAG2. Interestingly, two mutants showed opposing results for the ability to interact with core versus full length RAG2, indicating that the non‐core region of RAG2 participates in binding to core RAG1. Significantly, all of the RAG1 interdomain mutants demonstrated altered stoichiometries of the RAG complexes, with an increased number of RAG2 per RAG1 subunit compared to the wild type complex. Based on our results, we propose that interaction of RAG2 with RAG1 induces cooperative interactions of multiple binding sites, induced through conformational changes at the RAG1 interdomain boundary, and resulting in formation of the DNA cleavage active site.
The Impact of Government Ownership of Banks, Foreign Capital Inflows and Institutions on Financial Development

This thesis consists of three empirical and one theoretical essays on three determinants of financial development (FD) namely government ownership of banks, foreign capital inflows (FCI) and institutional quality. Some research has concluded that government ownership of banks negatively affects their soundness. Bretton Wood institutions have used these conclusions to advocate for state-owned banks privatization. The first essay shows that this research was weak in the way it controlled for fundamental determinants of soundness of banks, and lacked rigorous econometric analysis. With data covering 2001-2011, we show that if there is any relationship between government ownership of banks and their subsequent soundness, it is positive. These results are robust to various measures of FD, institutional quality and econometric approaches. The second essay presents a theoretical model predicting a negative relationship between Official Development Assistance (ODA) and FD when political institutions are weak. The third essay empirically investigates the hypothesis that the effects of ODA on FD are influenced by the level of democracy in recipient countries. Using a panel data for 37 developing countries covering 1980-2005, we apply different econometric approaches (pooled OLS, IV2SLS, fixed effects and dynamic GMM) to show that while ODA is harmful to FD in autocracies it could be effective in democracies. These results are robust to various measures of FD and democracy. The fourth essay is an empirical investigation of the hypothesis that different types of FCIs have different impacts on credit availability in developing countries. Using 5-year average data for 53 developing countries covering 1990-2013 and disaggregating FCIs into their main five types, we apply OLS, fixed effects, and dynamic GMM to show that there is a positive and statistically significant relationship between FDI, debt and equity and private credit while remittances and ODA are not significant determinants of private credit in developing countries.
Testing the Martingale Difference Hypothesis (MDH) with Structural Breaks: Evidence from Foreign Exchanges of Nigeria and South Africa

ABSTRACT This study tests for MDH in two prominent foreign exchange (FX) markets in Africa, Nigeria and South Africa using three benchmark currencies (euro, dollar and pound sterling). Data utilized cover time series closing rate data set of five-day weekly frequency spanning December 14, 2001 to September 26, 2014. The study considers both the linear and nonlinear measures for MDH with better size and power properties. We also capture structural break endogenously from the data stream using Perron (2006) unit root test with structural break. Three striking findings are discernible from our analyses. First, on average, the South African FX market appears to be more efficient than the Nigerian FX market. Thus, the latter may be more susceptible to speculations than the former. Second, ignoring significant structural breaks may render statistical inferences invalid. Third, the choice of methodology does matter when testing for MDH of foreign exchanges in Africa.