Miracle-dz/UniFAR-FTUs huggingface dataset:
Adverse Effects of Atypical Antipsychotic Agents and Their Effects on Quality of Life

Study Objectives. To determine how axis III metabolic disturbances associated with atypical antipsychotic agents (weight gain, diabetes mellitus, and hyperlipidemia) affect patients' quality of life by comparing perceived quality of life of patients taking these agents who developed the disorders with those who did not develop them. A secondary objective was to compare patients' assessments of their quality of life with assessments made of the same patients by their treating psychiatrists.
Sr2+ facilitates intermolecular G-quadruplex formation of telomeric sequences.

Electrophoretic and spectroscopic studies were made with the telomere-related sequences d(G4T2G4T2G4T2G4) (T2) and d(G4T4G4T4G4T4G4) (T4) in the presence of Na+, K+, and Sr2+. Electrophoretic evidence indicates that these two oligomers exist in multiconformational states in solutions. A band identified as that of intermolecular (tetramolecular) G-quadruplex is apparent in both T2 and T4, whereas a band identified as intramolecular (monomeric) G-quartet is only evident in T4. The remaining electrophoretic bands that exhibit mobilities intermediate of these two extremes are identified as those of hairpin-related duplexes and tetraplexes. In the presence of millimolar concentrations of Sr2+ and subsequent thermal treatment, the intensity corresponding to the band attributable to the intermolecular G-quadruplex is dramatically enhanced in T2 while those of the hairpin-related bands of intermediate mobility are greatly reduced. Similar but less dramatic enhancement of the intermolecular quadruplex band is also observed in T4. Although these effects can also be induced by K+, orders of magnitude higher concentrations are needed. The intensity of the intramolecular G-quartet band, apparent in T4 but not in T2, appears to be relatively insensitive to the type of cation present in the solution. These results demonstrate that both Sr2+ and K+ facilitate the intermolecular G-tetraplex formation, with the divalent cation being much more effective. Comparison with the corresponding CD spectral characteristics suggests that the electrophoretic intensity enhancement of the intermolecular G-quadruplex band is correlated to the intensity enhancement of of the positive CD maximum at 265 nm. (ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetics of mirodenafil and its two metabolites, SK3541 and SK3544, after intravenous and oral administration of mirodenafil to streptozotocin-induced diabetes mellitus rats

The area under the curve (AUC) of mirodenafil after intravenous administration in diabetes mellitus induced by streptozotocin (DMIS) rats was significantly smaller (by 28.0 %) than the control value, and the AUCSK3541/AUCmirodenafil ratio was significantly greater (by 130 %) in DMIS rats. This may be explained by the significantly faster hepatic CLint of mirodenafil, owing to increased hepatic CYP1A, CYP2B1/2, CYP2D, and CYP3A expression, and a faster hepatic blood flow rate, compared with control values. The AUC of mirodenafil after oral administration was comparable between DMIS and control rats, possibly because of the comparable intestinal CLint, which may be attributable to increased CYP1A2 expression and decreased CYP2D expression in the intestines of DMIS rats.
Successful Repeat Catheter Ablation of Recurrent Longstanding Persistent Atrial Fibrillation With Rotor Elimination as the Procedural Endpoint: A Case Series

There remains a lack of consensus regarding the ideal ablation strategy for atrial fibrillation (AF), particularly in patients with persistent or longstanding persistent AF. Given increasing evidence from clinical imaging studies that rotors sustain AF, rotor elimination may be a desirable procedural endpoint. However, there is no description to date of the clinical outcomes using rotor elimination during ablation as the procedural endpoint. Moreover, a series of studies question whether procedural AF termination is a desirable endpoint for ablation after many forms of AF ablation.
Union Business Leave Practices in Large U.S. Municipalities: An Exploratory Study

This article examines union business leave (UBL) or official time practices among the 77 largest municipalities in the United States. Specifically, it evaluates UBL practices as articulated in 231 collective bargaining agreements (CBAs) of police, firefighter, and nonsafety public employee unions. Results indicate that UBL is prevalent as 72% of unions receive some kind of UBL, most frequently paid leave financed by the city or through cost-sharing arrangements. Empirical findings suggest these practices are driven by political factors, and that resource constraints or the state or regional-level environment are nonsignificant. The article discusses these results and offers a series of policy recommendations.
Physical Factors Associated With Fatigue After Stroke: An Exploratory Study

Abstract Objective: To look for a relationship between physical fatigue and physical parameters in patients at least 3 months post stroke. Methods: We conducted a prospective cross-sectional study of 32 poststroke patients (average duration of stroke 40 months) who were recruited among in- and outpatients followed by the Department of Physical and Rehabilitation Medicine of a university hospital. Fatigue was defined as a Fatigue Severity Scale (FSS) score of 4 or more. The parameters studied were age, sex, time since stroke, Demeurisse Motor Index, Barthel Index score, new Functional Ambulation Category, Berg Balance Scale, 10-meter walk test, 6-minute walk test, Dijon Physical Activity Score, Montgomery and Asberg Depression Rating Scale, Epworth Sleepiness Scale, presence of pain, and length and area of the center of pressure displacement obtained posturographically. Results: Two-thirds of patients (65.6%) were fatigued. The mean FSS score was 4.3 ± 1.8. Fatigue was not associated with the physical parameters studied; notably, there was no correlation with motor impairment, autonomy and walking capacity, or balance and physical activity. However, after multivariate analysis, we found an association between physical fatigue and time since the occurrence of stroke (P = .05). Conclusions: Our study revealed a relationship between pain and physical fatigue, as reported by 2 other studies. Poststroke fatigue management should include appropriate pain management. Further studies are necessary to determine the causes of physical fatigue after stroke.
Behavior at the Local Level

Laboratory experiments have become a popular tool to learn about preferences and behavior. Classic laboratory games ordinarily have two characteristics. First, the players are anonymous, and second, they are strangers. This study subverts these characteristics to explore behavior when subjects play against identified members of their own social network. We play an ultimatum game in highly connected, rural villages in Sierra Leone. We randomly assign players to either the classic game or a modified game with revealed identity and compare behavior across these variations. We find that classic games do not translate well to behavior in the local context. Revealing the identity of the receiver leads to an increase in offers, supporting the idea that people care about revealed attributes, and that their average belief about one’s personal reputation exceeds the average belief about the reputation of the status quo. Variation in sizes of offers made increases in the version of the game with the most information revealed as would be expected if social relationships can be both good and bad. ∗Corresponding author: maarten.voors@wur.nl. We are indebted to the Gola Rainforest National Park and its partners (Government of Sierra Leone, Conservation Society of Sierra Leone and the Royal Society for the Protection of Birds), supported by the European Union and the Fonds Français pour l’Environnement Mondial. We thank Paul Richards, Erwin Bulte and Andreas Kontoleon for their collaboration. We thank N.W. O. grant # 453-10-001, ESRC and Cambridge University’s CCI for financial support. Thanks also to Esther Mokuwa, Koen Leuveld and our team of local enumerators for exceptional research assistance in Sierra Leone.
Problem Solving in Parkinson's Disease: Comparison of Performance on the Wisconsin and California Card Sorting Tests

Previous demonstrations that problem solving deficits may occur early in the course of Parkinson's disease (PD) have been taken to support the view that disturbances in the functioning of the frontal lobes are responsible for the initial cognitive deficits in this disease. However, no specific pattern of responding associated with poor problem solving by PD patients has been observed consistently. In an effort to clarify the nature of the problem solving deficits in PD we administered the Wisconsin Card Sorting Test (WCST) and the California Card Sorting Test (CCST), a new test which provides separate measures of concept generation, concept identification, and concept execution as well as several different measures of perseveration. On both tests PD patients of lower than normal mental status performed poorly and their patterns of performance resembled those previously described for patients with focal frontal lobe lesions, but PD patients of normal mental status performed normally. Because poor problem solving in association with increased perseverative responding was only observed for patients with global cognitive deficits these findings do not necessarily support the idea that frontal dysfunction is the principal cause of impaired cognition in PD. Although the overall pattern of results was similar for the WCST and the CCST, the CCST was more sensitive for detecting deficits than was the WCST. (J Geriatr Psychiatry Neurol 1990; 3:163-171).
THE EFFECTS OF ORGANIZATIONAL PRESTIGE ON ORGANIZATIONAL IDENTIFICATION: A CASE STUDY IN PRIMARY SCHOOLS

The aim of this study is to determine the relationship between organizational prestige and organizational identification perceptions of primary school teachers. In this study, in which the relationship between organizational prestige and organizational identification perception of primary school teachers was examined, the predictive correlational research model, which is one of the subcategories of correlational research models, has been used. Study group of the research constitutes of primary school teachers working in 34 primary schools located in Bolu central province as of 2017 academic year. Study group of the research constitutes of a total of 258 primary school teachers. The research data has been collected by the "Perceived Organizational Prestige Scale" and "Organizational Identification Scale. In the study, it was concluded that teachers' perceptions of organizational prestige were at "moderate" level. In the study, it was concluded that teachers' perceptions of organizational identification were at "moderate" level. In the research, it was found that there is a moderate and meaningful relationship between teachers' perceptions of the organizational prestige and organizational identification in the positive direction. Moreover, in the study, it was found out that organizational prestige is a significant predictor of organizational identification behaviors. Article visualizations:
Residue 2 of TIMP-1 Is a Major Determinant of Affinity and Specificity for Matrix Metalloproteinases but Effects of Substitutions Do Not Correlate with Those of the Corresponding P1′ Residue of Substrate*

The unregulated activities of matrix metalloproteinases (MMPs) are implicated in disease processes including arthritis and tumor cell invasion and metastasis. MMP activities are controlled by four homologous endogenous protein inhibitors, tissue inhibitors of metalloproteinases (TIMPs), yet different TIMPs show little specificity for individual MMPs. The large interaction interface in the TIMP-1·MMP-3 complex includes a contiguous region of TIMP-1 around the disulfide bond between Cys1 and Cys70 that inserts into the active site of MMP-3. The effects of fifteen different substitutions for threonine 2 of this region reveal that this residue makes a large contribution to the stability of complexes with MMPs and has a dominant influence on the specificity for different MMPs. The size, charge, and hydrophobicity of residue 2 are key factors in the specificity of TIMP. Threonine 2 of TIMP-1 interacts with the S1′ specificity pocket of MMP-3, which is a key to substrate specificity, but the structural requirements in TIMP-1 residue 2 for MMP binding differ greatly from those for the corresponding residue of a peptide substrate. These results demonstrate that TIMP variants with substitutions for Thr2 represent suitable starting points for generating more targeted TIMPs for investigation and for intervention in MMP-related diseases.
Histone H2B Monoubiquitination Mediated by HISTONE MONOUBIQUITINATION1 and HISTONE MONOUBIQUITINATION2 Is Involved in Anther Development by Regulating Tapetum Degradation-Related Genes in Rice1[OPEN]

Histone H2B monoubiquitination is essential for anther development. Histone H2B monoubiquitination (H2Bub1) is an important regulatory mechanism in eukaryotic gene transcription and is essential for normal plant development. However, the function of H2Bub1 in reproductive development remains elusive. Here, we report rice (Oryza sativa) HISTONE MONOUBIQUITINATION1 (OsHUB1) and OsHUB2, the homologs of Arabidopsis (Arabidopsis thaliana) HUB1 and HUB2 proteins, which function as E3 ligases in H2Bub1, are involved in late anther development in rice. oshub mutants exhibit abnormal tapetum development and aborted pollen in postmeiotic anthers. Knockout of OsHUB1 or OsHUB2 results in the loss of H2Bub1 and a reduction in the levels of dimethylated lysine-4 on histone 3 (H3K4me2). Anther transcriptome analysis revealed that several key tapetum degradation-related genes including OsC4, rice Cysteine Protease1 (OsCP1), and Undeveloped Tapetum1 (UDT1) were down-regulated in the mutants. Further, chromatin immunoprecipitation assays demonstrate that H2Bub1 directly targets OsC4, OsCP1, and UDT1 genes, and enrichment of H2Bub1 and H3K4me2 in the targets is consistent to some degree. Our studies suggest that histone H2B monoubiquitination, mediated by OsHUB1 and OsHUB2, is an important epigenetic modification that in concert with H3K4me2, modulates transcriptional regulation of anther development in rice.
Output Shocks In China: Do The Distributional Effects Depend On The Regional Source?

The tension between growth and inequality in the process of economic development has been recognised in the research literature as well as in policy-making circles for many decades. In few countries in the modern world is this problem more acute than in China where inter-provincial disparities are large by world standards and where remarkable economic growth in the past three decades has tended sooner to widen than to narrow them. Not surprisingly, the source of such inter-provincial disparities in China has been the subject of considerable research. Yet we have relatively little empirical knowledge of the effects on the provincial distribution of output of shocks to macroeconomic variables such as GDP. This is an important gap in the empirical literature: macroeconomic shocks are likely to have a differential impact on the provincial economies and so affect the provincial output distribution. Policy-makers need to know the sign, size and timing of such effects before making policy decisions designed to influence output at the national or regional level. In this paper we focus on the regional source of national shocks and ask whether the effect at the provincial level depends on the regional source of the shock. We use two alternative methods for this. The first is one recently employed by Chen and Groenewold (2015) to analyse the provincial effects of shocks to national output and investment using a restricted VAR model due to Lastrapes (2005). The method extends their work by disaggregating national GDP into three regional outputs – for the coastal, central and western regions of China. Our second method uses a sequence of VAR models, each with three regional outputs and one provincial output. We find that the two methods give remarkably similar results – both provide strong evidence that a shock to a particular region’s output has its main effects on the provinces in that region, although this is more marked in the short run than in the long run and differs somewhat across regions. In particular, a shock to national output which originates in the coastal region has an affect mainly on the coastal provinces in both the short and long runs. Such a shock is therefore likely to exacerbate existing inter-provincial disparities. However, there is more diffusion of the effects of a central shock, particularly in the long run which may help alleviate disparities. A shock to the western region also generates spillover effects in the long run although these are to the coastal provinces and will therefore likely widen existing disparities.
Intrapulmonary Delivery of CpG-ODN Microdroplets Provides Protection Against Escherichia coli Septicemia in Neonatal Broiler Chickens

SUMMARY Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine phosphodiester guanine (CpG) motifs (CpG-ODN) are effective immunostimulatory agents against a variety of viral, bacterial, and protozoan diseases in different animals including poultry. We have recently demonstrated that in ovo injection of CpG-ODN confers protection in neonatal chickens against bacterial septicemias. The objective of this study was to investigate the effectiveness of needle-free intrapulmonary (IPL) delivery of CpG-ODN microdroplets against Escherichia coli infection in neonatal chicks. In the present study, we used 880 chicks in total keeping 40 chicks per group. Chicks were delivered CpG-ODN or saline by IPL at the day 1 of hatch. Three days later, chicks were challenged with two doses (1 × 104 CFU, n = 20 or 1 × 105 CFU, n = 20) of E. coli. Chicks treated with CpG-ODN by the IPL route had significantly lower clinical signs and bacterial load compared to the group treated with saline (P < 0.05). CpG-ODN–treated groups were significantly protected against E. coli septicemia. We observed dose- and exposure time-dependent immunoprotective effects of IPL CpG-ODN in chicks. We found that IPL delivery of CpG-ODN can induce protective immunity as early as 6 hr that remains effective at least until day 5 post-treatment. Moreover, there were no adverse effects of IPL delivery of CpG-ODN on growth or mortality up to 42 days of age. Based on these findings, it can be suggested that CpG-ODN delivery by IPL route can be a promising alternative to antibiotics for inducing protective immunity in chicks during the critical first week of neonatal life.
Placental Transfer of Glucose and Amino Acids in Intrauterine Growth Retardation: Studies with Substrate Analogs in the Awake Guinea Pig

ABSTRACT: After experimentally inducing growth retardation by unilateral uterine artery ligation in midpreg-nancy, placental blood flow (PBF) (microsphere technique) and placental transfer of 14C-aminoisobutyric acid (AIB) and 3H-methylglucose (MG) were studied at d 44, 50, or 63 of gestation in 19 chronically catheterized awake guinea pigs. At d 44, fetal wt (FW) and placental wt were reduced by 16 and 18%, respectively, in the ligated horn and FW/PBF was increased by 122%. Placental efficiency to transfer MG and AIB (fetal dpm/g placenta) was maintained in the ligated horn, feto-placental extraction (feto-placental dpm/PBF) was increased, and placental transfer of the substrate analogs (fetal dpm/g fetus) was unchanged. At d 50 and 63, placental wt and FW were reduced in proportion (∼40%) in the growth-retarded group and FW/PBF was increased by 80 and 51%, respectively. Placental transfer of AIB was reduced by 33% at d 50 and by 18% at d 63. In addition, placental efficiency to transfer AIB was reduced by 36% at d 50 and by 22% at d 63 in the growth-retarded group. Fetal uptake of MG per g fetus was slightly reduced (–6%) at d 50 of gestation, but unaffected at d 63. Extraction of MG from the maternal PBF was increased, whereas the wt-specific transfer capacity of the placenta was unaltered. Our results demonstrate that experimental growth retardation in the guinea pig is associated with a substantial reduction of FW-specific placental transfer of AIB, indicating that the growth-retarded fetus has an impaired supply of amino acids during intrauterine life. This reduction is suggested to be due to alterations at the placental barrier level and will contribute to the development of intrauterine growth retardation independently of the PBF decrease per se. Placental transfer of MG per g fetus was only moderately reduced at d 50 of gestation, but otherwise maintained. Consequently, compromised placental glucose transfer is not likely to be the main cause of fetal hypoglycemia in guinea pig intrauterine growth retardation.
Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome

Noonan syndrome (NS) is the most common nonchromosomal genetic disorder associated with cardiovascular malformations. The most prominent cardiac defects in NS are pulmonary valve stenosis and hypertrophic cardiomyopathy. Gain-of-function mutations in the protein tyrosine phosphatase Shp2 have been identified in 50% of NS families. We created a NS mouse model with selective overexpression of mutant Shp2 (Q79R-Shp2) in the developing endocardial cushions. In our model, Cre recombinase driven by the Tie2 promoter irreversibly activates transgenic Q79R-Shp2 expression in the endothelial-derived cell lineage. Q79R-Shp2 expression resulted in embryonic lethality by embryonic day 14.5. Importantly, mutant embryos showed significantly enlarged endocardial cushions in the atrioventricular canal and in the outflow tract. In contrast, overexpression of wild-type Shp2 protein at comparable levels did not enhance endocardial cushion growth or alter the morphology of the mature adult valves. Expression of Q79R-Shp2 was accompanied by increased ERK1/2 activation in a subset of cells within the cushion mesenchyme, suggesting that hyperactivation of this signaling pathway may play a pathogenic role. To test this hypothesis in vivo, Q79R-Shp2-expressing mice were crossed with mice carrying either a homozygous ERK1 or a heterozygous ERK2 deletion. Deletion of ERK1 completely rescued the endocardial cushion phenotype, whereas ERK2 protein reduction did not affect endocardial cushion size. Constitutive hyperactivation of ERK1/2 signaling alone with a transgenic approach resulted in a phenocopy of the valvular phenotype. The data demonstrate both necessity and sufficiency of increased ERK activation downstream of Shp2 in mediating abnormal valve development in a NS mouse model.
Roles of OX40 in the Pathogenesis and the Control of Diseases

OX40 belongs to the tumor necrosis factor receptor superfamily, and its expression is restricted to activated T-cells. Ligation of OX40 during T-cell-dendritic cell interaction is crucial for clonal expansion of antigen-specific T-cells and generation of T-cell memory. The ligand of OX40 (OX40L) is expressed not only on dendritic cells but also on other cell types, such as B-cells, vascular endothelial cells, natural killer cells, and mast cells. The pathophysiological relevance of this broad distribution needs further investigation. In particular, OX40L on vascular endothelial cells may play a role in inflammatory vasculitis as well as in atherosclerotic change. Recent studies with animal models have indicated the critical involvement of OX40 in the pathogenesis of a variety of immunologic abnormalities of inflammatory, autoimmune, infectious, allergic, and allotransplantation-Related diseases. Blockade of OX40-OX40L interaction has been shown to prevent, cure, or ameliorate these diseases. In contrast, activation of OX40 is known to break an existing state of tolerance in malignancies, leading to a reactivation of antitumor immunity. These findings clearly suggest that the OX40/OX40L system is one of the most promising targets of immune intervention for treatment of these diseases.