Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between the CYP2C9 polymorphism and the drug metabolism phenotype

Abstract CYP2C9, an isoform of the cytochrome P450 enzyme, is involved in the metabolism of most of the drugs of choice for the treatment of thromboembolic disorders. Functional polymorphism is associated with two variant alleles (alleles *2 and *3) encoding CYP2C9 enzymes with a potentially different catalytic activity. The aim of the study was to determine the frequency of the CYP2C9 polymorphism in a representative sample of the Croatian population (n=177) and to assess the association between the CYP2C9 polymorphism and the warfarin dose in patients with thromboembolism (n=181). The CYP2C9 genotype was determined by polymerase chain reaction-restriction fragment length poymorphism (PCR-RFLP). According to the CYP2C9 genotype distribution, 31.2% of the healthy subjects were identified with a heterozygous or homozygous CYP2C9 variant genotype. The frequency of 2C9*2 and 2C9*3 alleles was 12.4% and 3.7%, respectively. There was no gender-related genotype or allele difference. In thromboembolism patients, the frequency of CYP2C9 alleles *2 and *3 was 17.4% and 6.6%, respectively, and did not differ significantly from the control group. Almost half (42.5%) of the patients carried at least one variant CYP2C9 genotype. The allele difference between patient subgroups receiving warfarin doses lower and higher than the optimal warfarin dose (4.1 mg/day) was significant (p=0.027), especially for allele 2C9*3 (p=0.019; OR 3.250, 95%, CI 1.263–8.413). Comparison of the warfarin dose between patients with different genotypes yielded a significant dose difference between the patients with wild-type genotype and those with variant genotypes (Kruskall-Wallis, χ2=9.745, p=0.008). The results of the association of each of five genotype combinations with the warfarin maintenance dose revealed it to be significantly related to the genotype (Kruskall-Wallis, χ2=12.854, p=0.025). Expressed as percentage of the mean dose in patients with wild-type alleles, the mean warfarin maintenance dose was 92% in 2C9*2 heterozygotes, 74% in 2C*3 heterozygotes, 61% in 2C9*2 homozygotes, 34% in 2C9*3 homozygotes and 63% in compound heterozygotes for 2C9*2 and 2C9*3. Although the mean maintenance dose in homozygous *2/*2 and compound *2/*3 genotype patients was markedly lower (mean 2.66 mg and 2.75 mg, respectively, vs. 4.37 mg), statistical analysis yielded no significance because of the small number of patients carrying these genotypes. A significantly lower maintenance dose was observed in the subgroup of heterozygous *1/*3 genotype patients (p=0.022). These preliminary results suggest a significant association of the CYP2C9 polymorphism with the warfarin dose and underline the importance of pre-therapeutic genotyping to identify the subjects likely to develop undesirable drug effects.
Assessment of executive functioning in children after TBI with a naturalistic open-ended task: A pilot study

Purpose: Traumatic brain injury (TBI) often leads to executive functions (EF) deficits, resulting in severe longstanding disabilities in daily life activities. The sensitivity and ecological validity of neuropsychological tests have been questioned. The aim of this study was to pilot a novel open-ended naturalistic task and to compare it to other standardized assessments of EF in children post-TBI. Methods: Ten children aged 8–14, with moderate-to-severe TBI, and 18 matched controls participated in the study. The clinical group was assessed using cognitive tests and parent-based questionnaires of EF. An interactive ecological cooking task was designed. Results: Analyses indicated mild-to-moderate executive deficits in the cognitive tests in approximately half of the TBI group. For the experimental cooking task, all quantitative and qualitative variables were significantly impaired for the TBI group compared to the control group and failure in the cooking task was associated with lower scores in cognitive tests of EF. The task was able to discriminate the TBI children from the control group. Conclusion: This pilot study highlights the role of naturalistic assessments, to complement standardized tests in assessing patients’ dysexecutive impairments in complex activities of daily living post-childhood TBI.
Postoperative Facial Nerve Function in Pediatric Parotidectomy

Objective To analyze the incidence of postparotidectomy facial nerve dysfunction in pediatric patients and to evaluate the association between patient demographics or underlying pathology and functional outcomes. Study Design Case series with chart review. Setting Tertiary-care pediatric hospital. Subjects and Methods We reviewed charts of patients younger than 18 years who underwent parotidectomy performed by a pediatric otolaryngologist between 1999 and 2011 at a tertiary pediatric center. Distributions of postoperative facial nerve dysfunction and timing of recovery were noted. Chi-square and t-test analyses were conducted to determine the association between demographics or pathology and functional outcomes. Results Forty-three patients met inclusion criteria: 41 underwent superficial parotidectomy, and 2 underwent total parotidectomy. Leading indications for surgery were atypical mycobacterial infection (16/43 [37.2%]) and first branchial cleft anomaly (8/43 [18.6]). The facial nerve was sacrificed in 1 (2%) patient with Ewing’s sarcoma involving the nerve. The incidence of immediate facial nerve paresis was 21% (9/43), involving the marginal mandibular nerve (n = 7), buccal branch (n = 1), and both marginal mandibular and frontal branches (n = 1). Full recovery of nerve function in patients with paresis occurred within 1 month (n = 2), 2 months (n = 1), 6 months (n = 3), or 10 months (n = 2). Conclusion Postparotidectomy paresis of distal branches of the facial nerve is a common occurrence in the pediatric population and should be discussed during preoperative evaluation. The risk is comparable to that of the adult population. Age, gender, and pathologic diagnosis were not predictive of postoperative nerve dysfunction.
In vitro stimulation of naive mouse lymphocytes by Heligmosomoides polygyrus adult worm antigens induces the production of IgG1

The production of high levels of IgG1, by mice chronically infected with the parasitic nematode Heligmosomoides polygyrus, has been documented for a number of years. In order to investigate this phenomenon, naive lymphocytes from B10.D2 mice were incubated in vitro with H. polygyrus adult worm homogenate (AWH) and the culture supernatants examined for immunoglobulin production. Stimulation of pooled naive splenocytes by AWH was found to produce IgG1, but not IgM, in an antigen dose dependent manner. Identical stimulation of splenocytes of individual inbred mice, indicated that this effect was reproducible but with considerable variation between mice. When the IgG1 produced was tested for specificity, it was found that there was little evidence that the immunoglobulin produced was able to bind to the inducing parasite antigens. Analysis of purified T cells reconstituted with splenocytes, demonstrated that T cells were the target lymphocytes of the stimulating molecule, contained within AWH. These results show that H. polygyrus AWH can induce the production of non‐parasite specific IgG1 from naive splenocytes and that this production is crucially dependent upon the cell content of the in vitro culture. Furthermore, the production of IgG1 is not proportional to the degree of lymphocyte proliferation. It is suggested that at least part of the hypergammaglobulinaemia produced during a primary H. polygyrus infection, is due to this non‐specific stimulation of mouse lymphocytes by the parasite.
Saving Behavior and Housing Wealth Evidence from German Micro Data

Abstract Housing property is the most important position in a household’s wealth portfolio. Even though there is strong evidence that house price cycles and saving patterns behave synchronously, the underlying causes remain controversial. The present paper examines if there is a wealth effect of house prices on savings using household-level panel data from the German Socio-Economic Panel for the period 1996-2012. We find that young homeowners decrease their savings in response to unanticipated house price shocks, whereas old households hardly respond to house price changes. Although effects are relatively low in magnitude, we interpret this as evidence of a housing wealth effect.
Introduction to Quantitative Methods

Introduction and Aim The aim of this seminar is to give researchers in sociology and political sciences practical knowledge of the application of basic quantitative techniques, which are commonly used in sociology and political sciences, while using one of the major statistical software packages STATA. The seminar centers on the linear regression model. A correct understanding of its proper functioning and limitations is an essential precondition for venturing into more advanced techniques. It also provides an introduction to the logistic regression model. In this seminar, therefore, you can expect to learn: How to estimate a multivariate linear regression model and interpret correctly its results How to estimate and correctly interpret interaction effects How to apply regression diagnostics tools How to estimate a logistic regression and interpret its results
Foreign Direct Investment and Poverty Reduction

It is widely proclaimed that capital account liberalization would immensely benefit developing economies because once capital controls are lifted, developing economies create a potential for movement of capital. And, this free movement of capital could possibly increase growth thereby lifting millions out of poverty. India has been gradually liberalizing since the 1980s and throughout more capital inflows were observed compared to outflows. Also, the composition of capital flows has been changing since the 1980s–with Foreign Direct Investment (FDI) inflows rising steadily post-1991compared to portfolio and debt flows. However, since 2000, FDI outflows from India were also witnessed. In this paper we empirically test the impact of FDI flows on poverty in India for 1980–2011. To provide a correct perspective to India’s performance we also analyze the link between FDI flows and poverty for SAARC countries. For a better understanding of how FDI flows impact poverty, we analyze the outflows and inflows separately. The results show both similarities and contrasts in the behaviour of India in comparison with the other SAARC countries.
Contemporary Capitalism: The Variety and Unequal Performance of Really Existing Markets: Farewell to Doctor Pangloss?

A RETURN TO FREE MARKET CONCEPTIONS: WHY? The conceptions about the self-regulating mechanisms associated with markets have undergone the equivalent of a long wave. During the Great Depression of the 1930s, a majority of economists were critical of the institutional impediments to the free functioning of markets. Only a minority argued that it was in the very nature of free markets to trigger large instabilities and/or stagnation (Weir and Skocpol, 1985). After World War II, the Keynesian heterodoxy became the core of significant revolution concerning the respective roles that the state and market should play in the long run social and economic reproduction of capitalism: Adequate public regulation and fine tuning of monetary and fiscal policies could promote quasifull employment, along a steady growth path. Basically market mechanisms had to be tamed by a series of legislation, regulation, and collective agreements, as well as built-in stabilizers in the tax system and/or in the reaction functions of central banks. As Joan Robinson recurrently pointed out, markets were efficient for allocating scarce resources between alternative goals via the formation of relative prices. But one major drawback resulted from the fact that pure market mechanisms were generally unable to provide full employment and macroeconomic stability. In fact during the fifties and sixties this view was widely shared by almost all governments, including the most conservative ones. Did not Richard Nixon declare, “Now we are all Keynesians”?
Fractures of the Olecranon in Children. Long-Term Follow-Up of 39 Cases

Thirty-nine patients, who had received a fracture of the olecranon at an average age of 7.4 years, were reviewed at an average age of 32 years, in order to evaluate the results of treatment. All patients had reached skeletal maturity at follow-up. Thirty-four fractures were treated conservatively and five, surgically. Of the 34 fractures treated conservatively, six also had surgical treatment of associated fractures. We identified five patterns of fracture on the basis of the anatomic site of the fracture line, the interfragmentary displacement and the presence of an associated lesion. According to our grading scale, 34 patients had a good result, two a fair result and three a poor result. We observed poor results in only 7.6% of cases, even though 85% of the patients had received an intraarticular fracture. We believe that the long-term prognosis of olecranon fractures in children is related to the anatomic site of the fracture line, to the interfragmentary displacement and to the presence of an associated lesion. Conservative treatment may be indicated when the interfragmentary displacement is less than 2 mm. The presence of an associated lesion is a negative prognostic factor.
The power and perils of ‘molecular taxonomy’: a case study of eyeless and endangered Cicurina (Araneae: Dictynidae) from Texas caves

Rapid development in karst‐rich regions of the US state of Texas has prompted the listing of four Cicurina species (Araneae, Dictynidae) as US Federally Endangered. A major constraint in the management of these taxa is the extreme rarity of adult specimens, which are required for accurate species identification. We report a first attempt at using mitochondrial DNA (mtDNA) sequences to accurately identify immature Cicurina specimens. This identification is founded on a phylogenetic framework that is anchored by identified adult and/or topotypic specimens. Analysis of ~1 kb of cytochrome oxidase subunit I (CO1) mtDNA data for over 100 samples results in a phylogenetic tree that includes a large number of distinctive, easily recognizable, tip clades. These tip clades almost always correspond to a priori species hypotheses, and show nonoverlapping patterns of sequence divergence, making it possible to place species names on a number of immature specimens. Three cases of inconsistency between recovered tip clades and a priori species hypotheses suggest possible introgression between cave‐dwelling Cicurina, or alternatively, species synonymy. Although species determination is not possible in these instances, the inconsistencies point to areas of taxonomic ambiguity that require further study. Our molecular phylogenetic sample is largest for the Federally Endangered C. madla. These data suggest that C. madla occurs in more than twice the number of caves as previously reported, and indicate the possible synonymy of C. madla with C. vespera, which is also Federally Endangered. Network analyses reveal considerable genetic divergence and structuring across caves in this species. Although the use of DNA sequences to identify previously ‘unidentifiable’ specimens illustrates the potential power of molecular data in taxonomy, many other aspects of the same dataset speak to the necessity of a balanced taxonomic approach.
Effects of Tandospirone on “5-HT1A Receptor-Associated Symptoms” in Patients with Machado-Josephe Disease: An Open-Label Study

BackgroundWe investigated the frequencies of the symptoms such as “ataxia, depression, insomnia, anorexia, and pain,” that have been reported to be associated with 5-HT1A receptor, and the effect of tandospirone citrate (tandospirone: 5-HT1A agonist) in patients with Machado-Joseph disease (MJD). MethodsTen MJD patients received tandospirone (15-30mg/d) for seven weeks. During that time, they were evaluated weekly using the Ataxia Rating Scale (ARS) and Total Length Traveled (TLT) by Stabilimetry tests, the Self-rating Depression Scale (SDS), which in addition to evaluating their level of depression, also evaluated their degree of insomnia and anorexia, and a pain questionnaire. ResultsBefore tandospirone therapy, all patients displayed cerebellar ataxia, while insomnia, and leg pain was observed in 7 patients, depression in 6 patients, and anorexia was observed in 2 patients. In response to treatment, 7 of the 10 patients who were ataxic showed a reduction in their ARS, while 3 of 6 patients showed a reduction in their SDS, and 5 of 7 patients showed an alleviation of their insomnia and leg pain. Both of the affected patients showed a marked improvement in their anorexia. A stabilimetry test could be performed in 7 patients, 5 of whom showed a reduction in TLT. ConclusionsOur data indicate that the patients with MJD are prone to manifest 5-HT1A receptor-associated symptoms, and tandospirone is a useful drug for these symptoms in patients with MJD, though a double-blind study is needed.
Conformational maturation of CFTR but not its mutant counterpart (delta F508) occurs in the endoplasmic reticulum and requires ATP.

Metabolic labeling experiments followed by immunoprecipitation were performed to investigate the kinetics, location and inhibitor sensitivity of degradation of both wild‐type (wt) and mutant (delta F508) cystic fibrosis conductance transmembrane regulator (CFTR). At the earliest stages of the biosynthetic process, both wt and delta F508 CFTR were found to be susceptible to degradation by endogenous proteases. Virtually all delta F508 CFTR and 45‐80% of wt CFTR were rapidly degraded with a similar half‐life (t1/2 approximately 0.5 h). The remaining wt CFTR attained a protease‐resistant configuration regardless of whether traffic between the endoplasmic reticulum (ER) and Golgi was operational. Metabolic energy is required for the conformational transition, but not to maintain the stability of the protease‐resistant wt CFTR. Intracellular degradation of delta F508 CFTR and of incompletely folded wt CFTR occurs in a non‐lysosomal, pre‐Golgi compartment, as indicated by the sensitivity of proteolysis to different inhibitors and temperature. Accordingly, products of the degradation of delta F508 CFTR could be detected by immunoblotting in isolated ER, but not in the Golgi. Together, these results suggest a dynamic equilibrium between two forms of wt CFTR in the ER: an incompletely folded, protease‐sensitive form which is partially converted by an ATP‐dependent process to a more mature form that is protease‐resistant and capable of leaving the ER. The inability delta F508 CFTR to undergo such a transition renders it susceptible to complete and rapid degradation in a pre‐Golgi compartment.
A longitudinal study of personality and major depression in a population-based sample of male twins

ABSTRACT Background The relationship between personality and psychiatric illness is complex. It is not clear whether one directly causes the other. Method In a population-based sample of male twins (n=3030), we attempted to predict major depression (MD) from neuroticism (N) and extraversion (E) and vice versa, to evaluate the causal, scar, state, and prodromal hypotheses. In a longitudinal, structural equation twin model, we decomposed the covariation between N and MD into (a) genetic and environmental factors that are common to both traits, as well as specific to each one and (b) direct causal effects of N at time 1 on subsequent MD, as well as between MD and subsequent N. Results E was negatively correlated with lifetime and one-year prevalence of MD. N predicted the new onset of MD, and was predicted by both current and past MD. It did not predict the time to onset of MD. All of the covariation between N and MD was due to additive genetic and individual-specific environmental factors shared by both traits and a direct causal path between MD and N assessed later. No genetic factors were unique to either trait. Conclusions In men, N may be a vulnerability factor for MD but does not cause it directly. However, MD may have a direct causal effect on N. The genetic overlap between N and MD in men may be greater than in women.
Enhanced signaling through the IL-2 receptor in CD8+ T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+ T cells rather than promotion of cell death

Multiple cytokines, including IL-2, can affect T cell proliferation and survival. However, IL-2 can lead to apoptosis as well as proliferation, making unclear whether IL-2 receptor (IL-2R) signals ultimately have a predominantly positive or negative effect. To address this issue, we examined the effect of enhancing IL-2R signals in CD8+ T cells after antigen stimulation by engineering a transgenic (Tg) mouse strain with CD8+ T cells capable of augmented, regulated, autocrine IL-2R signaling after target recognition by means of expression of a chimeric granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-2R. The Tg CD8+ T cells can bind the granulocyte-macrophage colony-stimulating GM-CSF produced by antigen stimulation, but the GM-CSF binding results in delivery of an IL-2R signal. After antigen stimulation in vivo, the Tg T cells demonstrated marked increases in the initial proliferative response and cell expansion and displayed continued increases in cell expansion after repeated antigen exposure. These data suggest that the predominant role of IL-2R signals delivered to responding CD8+ T cells is to set the size of the initial response to antigen by promoting T cell proliferation and survival and not cell death.
Understanding the experience of teachers in a professional learning community: a case study of an interdisciplinary ninth grade team.

Professional learning communities (PLCs) have the potential to improve pedagogy (Dufour, 2004), build community in schools, (Huffman, 2011), allow teachers to develop innovative ideas (Cornelius, 2011) and “create and sustain a culture of learning for all students” (Huffman, 2011, p. 321). Because of these advantages, schools throughout the United States have implemented PLCs. While there has been some success with these initiatives, schools have faced many challenges in realizing the potential benefits associated with PLCs. The purpose of this qualitative case study is to understand how teachers experience participation in a professional learning community. Research questions focused on understanding school contextual factors, how teachers describe their experiences as part of a PLC, and how teachers’ practices have been influenced by their participation on the PLC. Findings revealed that institutional and cultural factors positively impact the collaborative work of the professional learning community; participation in the ninth grade interdisciplinary PLC provides increased teacher support, a higher degree of teacher empowerment, and leads to increased teacher capacity and sense of selfefficacy; and participation on the ninth grade interdisciplinary PLC results in increased support for students and stronger teacher-student relationships. The study’s findings also suggest the importance of administrative support and guidance throughout the PLC process in order to maximize the potential benefits of PLCs.