Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence of and motives for pharmacological neuroenhancement in Switzerland--results from a national Internet panel.

AIMS To estimate the prevalence of self-reported pharmacological neuroenhancement (PNE) with prescription or recreational drugs among the Swiss general population and correlates of PNE. DESIGN A population-based cross-sectional study using a self-administered online survey. SETTING A telephone-recruited highly representative internet panel in Switzerland. PARTICIPANTS A total of 10,171 Swiss employees and students (unweighted n = 10,084) aged 15-74 years (mean age: 39.1 ± 13.3; 46.6% female). MEASUREMENTS Self-reported life-time, past-year and past-month use of prescription or recreational drugs for PNE, motives for use and correlates of PNE, including socio-demographic, health and recreational drug use characteristics. FINDINGS The life-time prevalence of PNE was 4.0% [95% confidence interval (CI) = 3.62, 4.38], and the past-year prevalence was 2.1% (95% CI = 1.82, 2.38). Life-time pharmacological mood enhancement (3.1%; 95% CI = 2.76, 3.44) was more prevalent than pharmacological cognitive enhancement (1.4%; 95% CI = 1.17, 1.63). Fifty-four participants reported both (0.5%; 95% CI = 0.36, 0.64). PNE was associated with studying rather than full-time [odds ratio (OR) = 0.35; 95% CI = 0.21, 0.57] or part-time employment (OR = 0.39; 95% CI = 0.23, 0.67), stress (OR = 1.51 95% CI = 1.31, 1.75), cocaine (OR = 2.40; 95% CI = 1.51, 3.82) and amphetamine use (OR = 2.44; CI 95% = 1.37, 4.33), diagnosis of a mental disorder (OR = 4.26; 95% CI = 3.14, 5.80), and perceived poor health (OR = 0.76; 95% CI = 0.64, 0.90). CONCLUSIONS Taking prescription or recreational drugs for pharmacological neuroenhancement is rare among Swiss employees and students (4.0%). Pharmacological mood enhancement (3.1%) is more prevalent than direct pharmacological cognitive enhancement (1.4%).
Intestinal trehalase activity in a UK population: establishing a normal range and the effect of disease

Trehalose is a disaccharide, the main dietary source being mushrooms. It has been approved as an additive in the preparation of dried food. Isolated intestinal trehalase deficiency is found in 8 % of Greenlanders, but is rare elsewhere. The normal range of trehalase activity and the incidence of isolated trehalase deficiency in the UK have not been reported. Patients (n 400) were investigated for suspected malabsorption. Endoscopic distal duodenal biopsies were taken for histological assessment and maltase, sucrase, lactase and trehalase estimation. Disaccharidase activities were determined by Dahlqvist's technique (). Most patients (n 369) had normal duodenal histology. In these, square root transformation of trehalase activity produced a normal distribution. The normal range (mean ± 2 SD) was 4·79–37·12 U/g protein. One patient had an isolated borderline trehalase deficiency. The thirty-one patients with villous atrophy had significantly reduced disaccharidase activities. With ingestion of a gluten-free diet, maltase, sucrase and trehalase activities recovered to normal in most patients, whereas lactase activity did not. The normal range and very low incidence of isolated enzyme deficiency is comparable with that described in populations from the USA and mainland Europe. Activity is significantly reduced in untreated coeliac disease and recovers with treatment with a gluten-free diet. There is no place for routine determination of trehalase activity in the UK population and there should be no concern over the introduction of trehalose-containing dried foods.
Does farm size matter? Investigating scale efficiency of peasant rice farmers in northern Ghana

The study assessed the technical and scale efficiency of small-scale rice producers in northern Ghana as well as the effect of farm size on efficiency. Using survey data from 300 farm households, the study employed data envelopment analysis (DEA) to measure efficiency and a bootstrapped truncated regression in the second stage to assess the determinants of efficiency. The results indicated that respondents had overall technical efficiency of 46.6 percent, pure technical efficiency of 65.1 percent and scale efficiency of 69.5 percent. Farm size had a significantly positive effect on scale efficiency with majority of the farms operating at increasing returns to scale. The determinants of efficiency included farm size, gender of the household head, access to credit and irrigation, number of extension visits, the degree of specialization in rice production and location of the farm. Most of the inefficiencies are either technical or scale in nature hence there is justification to increase the scale of production of smaller farms in order to take advantage of unexplored economies of scale. The technically inefficient farmers also need to reduce waste in resource utilization by improving their efficiency of resource use. The authors prescribe other policy measures needed to improve rice production in northern Ghana.
Cysteinyl‐leukotriene receptor activation in brain inflammatory reactions and cerebral edema formation: a role for transcellular biosynthesis of cysteinyl leukotrienes

We studied the effect of intravascular activation of human neutrophils on the synthesis of cysteinyl leukotrienes (cysLT) and the formation of cerebral edema in guinea‐pig brains. Challenge with the chemotactic formylated tripeptide fMLP (0.1 µM) of neutrophil‐perfused brain in vitro resulted in blood‐brain barrier disruption associated with a significant increase of cysLT. Both events were completely prevented by neutrophil pretreatment with a specific 5‐lipoxygenase (5‐LO) inhibitor. Perfusion with the 5‐LO metabolite leukotriene B4 (10 nM), together with neutrophils treated with the 5‐LO inhibitor, did not restore the alteration in permeability observed upon perfusion with untreated and activated neutrophils. The dual cysLT1‐cysLT2 receptor antagonist BAYu9773 was more potent and more effective than a selective cysLT1 antagonist in preventing the brain permeability alteration induced by neutrophil activation. RT‐PCR showed significant expression of cysLT2 receptor mRNA in human umbilical vein endothelial cells. Intravital microscopy in mice showed that inhibition of leukotriene synthesis significantly reduced firm adhesion of neutrophils to cerebral vessels without affecting rolling. These data support the hypothesis that neutrophil and endothelial cells cooperate toward the local synthesis of cysLT within the brain vasculature and, acting via the cysLT2 receptor on endothelial cells, may represent a contributing pathogenic mechanism in the development of cerebral inflammation and edema.
FTY720 Phosphate Activates Sphingosine-1-Phosphate Receptor 2 and Selectively Couples to Gα12/13/Rho/ROCK to Induce Myofibroblast Contraction

FTY720 phosphate (FTY720-P; 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol, monodihydrogen phosphate ester) is a nonselective sphingosine-1-phosphate (S1P) receptor agonist thought to be devoid of activity at the S1P2 receptor subtype. However, we have recently shown that FTY720-P displays significant S1P2 receptor agonist activity in recombinant cells and fibroblasts expressing endogenous S1P2 receptors. To elucidate the S1P2-dependent signaling pathways that were activated by FTY720-P, we employed second messenger assays and impedance-based assays in combination with pharmacological and small interfering RNA–based pathway inhibition in recombinant Chinese hamster ovary (CHO)–S1P2 cells as well as human lung myofibroblasts generated in vitro. In CHO-S1P2 cells, FTY720-P did not modulate cAMP or calcium levels. However, reporter-gene assays, impedance-based assays with a selective Rho-associated kinase (ROCK) inhibitor, Gα12/13 knockdown and activated Rho–pull-down assays demonstrated that FTY720-P potently activated Gα12/13/Rho/ROCK signaling. S1P similarly activated Gα12/13/Rho/ROCK signaling via S1P2 receptors, whereas the two selective S1P1 receptor agonists (Z,Z)-5-(3-chloro-4-[(2R)-2,3-dihydroxy-propoxy]-benzylidene)-2-propylimino-3-o-tolyl-thiazolidin-4-one (ponesimond) and 5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-3-[3-(trifluoromethyl)phenyl]1,2,4-oxadiazole (SEW2871) were inactive. In lung myofibroblasts, which mainly expressed the S1P2 receptor subtype, we showed that FTY720-P selectively activated the Gα12/13/Rho/ROCK pathway via the S1P2 receptor. Moreover, the activation of the Gα12/13/Rho/ROCK pathway in myofibroblasts by FTY720-P caused potent myofibroblast contraction similar to that induced by the natural ligand S1P. Thus, complementing second messenger assays with unbiased label-free assays or phenotypic assays in native expression systems can uncover activation of additional pathways, such as Gα12/13/Rho/ROCK signaling.
A trans-Dominant Form of Gag Restricts Ty1 Retrotransposition and Mediates Copy Number Control

ABSTRACT Saccharomyces cerevisiae and Saccharomyces paradoxus lack the conserved RNA interference pathway and utilize a novel form of copy number control (CNC) to inhibit Ty1 retrotransposition. Although noncoding transcripts have been implicated in CNC, here we present evidence that a truncated form of the Gag capsid protein (p22) or its processed form (p18) is necessary and sufficient for CNC and likely encoded by Ty1 internal transcripts. Coexpression of p22/p18 and Ty1 decreases mobility more than 30,000-fold. p22/p18 cofractionates with Ty1 virus-like particles (VLPs) and affects VLP yield, protein composition, and morphology. Although p22/p18 and Gag colocalize in the cytoplasm, p22/p18 disrupts sites used for VLP assembly. Glutathione S-transferase (GST) affinity pulldowns also suggest that p18 and Gag interact. Therefore, this intrinsic Gag-like restriction factor confers CNC by interfering with VLP assembly and function and expands the strategies used to limit retroelement propagation. IMPORTANCE Retrotransposons dominate the chromosomal landscape in many eukaryotes, can cause mutations by insertion or genome rearrangement, and are evolutionarily related to retroviruses such as HIV. Thus, understanding factors that limit transposition and retroviral replication is fundamentally important. The present work describes a retrotransposon-encoded restriction protein derived from the capsid gene of the yeast Ty1 element that disrupts virus-like particle assembly in a dose-dependent manner. This form of copy number control acts as a molecular rheostat, allowing high levels of retrotransposition when few Ty1 elements are present and inhibiting transposition as copy number increases. Thus, yeast and Ty1 have coevolved a form of copy number control that is beneficial to both “host and parasite. ” To our knowledge, this is the first Gag-like retrotransposon restriction factor described in the literature and expands the ways in which restriction proteins modulate retroelement replication.
Automated Neuromelanin Imaging as a Diagnostic Biomarker for Parkinson's Disease

We aimed to analyze the diagnostic accuracy of an automated segmentation and quantification method of the SNc and locus coeruleus (LC) volumes based on neuromelanin (NM)‐sensitive MRI (NM‐MRI) in patients with idiopathic (iPD) and monogenic (iPD) Parkinson's disease (PD).
Survey of underground cable generated magnetic fields in a residential subdivision

Increasingly dense residential housing developments have spurned new concerns about electromagnetic fields. A survey of the magnetic fields generated by the distribution system in such a residential subdivision is performed. The magnetic fields above the underground cables, around the transformers and junction boxes, and at the service entrance panels are measured. The largest magnetic fields of 95 mG and 148 mG are recorded at the surfaces of the transformer enclosures and junction boxes, respectively, at around 30% to 40% of full load. It is also observed that magnetic fields reduce to less than 3 mG at a distance of ~1 m from the distribution system infrastructure. To support estimations of peak magnetic fields at full load conditions, software is developed to model the magnetic field generated by the underground cables composed of twisted conductors.
Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment

Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18–25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake.
Is It Better to Govern Managers via Agency or Stewardship? Examining Asymmetries by Family Versus Nonfamily Affiliation

This article examines whether agency or stewardship is the more effective form of managerial governance within family firms. Synthesizing arguments regarding the differential tendencies of nonfamily versus family managers and the bifurcated manner in which they are likely to be governed, we propose asymmetric responses to agency versus stewardship mechanisms. Our empirical results provide evidence challenging common assumptions regarding the behavior exhibited by nonfamily versus family managers and the mechanisms by which each is governed. Although our findings also provide evidence of response asymmetry, they nevertheless point to the greater effectiveness of stewardship over agency governance irrespective of a manager’s family affiliation.
Differential Effects of TBC1D15 and Mammalian Vps39 on Rab7 Activation State, Lysosomal Morphology, and Growth Factor Dependence*

The small GTPase Rab7 promotes fusion events between late endosomes and lysosomes. Rab7 activity is regulated by extrinsic signals, most likely via effects on its guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP). Based on their homology to the yeast proteins that regulate the Ypt7 GTP binding state, TBC1D15, and mammalian Vps39 (mVps39) have been suggested to function as the Rab7 GAP and GEF, respectively. We developed an effector pull-down assay to test this model. TBC1D15 functioned as a Rab7 GAP in cells, reducing Rab7 binding to its effector protein RILP, fragmenting the lysosome, and conferring resistance to growth factor withdrawal-induced cell death. In a cellular context, TBC1D15 GAP activity was selective for Rab7. TBC1D15 overexpression did not inhibit transferrin internalization or recycling, Rab7-independent processes that require Rab4, Rab5, and Rab11 activation. TBC1D15 was thus renamed Rab7-GAP. Contrary to expectations for a Rab7 GEF, mVps39 induced lysosomal clustering without increasing Rab7 GTP binding. Moreover, a dominant-negative mVps39 mutant fragmented the lysosome and promoted growth factor independence without decreasing Rab7-GTP levels. These findings suggest that a protein other than mVps39 serves as the Rab7 GEF. In summary, although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence.
Role of 108 schizophrenia‐associated loci in modulating psychopathological dimensions in schizophrenia and bipolar disorder

The Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) identified 108 loci associated with schizophrenia, but their role in modulating specific psychopathological dimensions of the disease is unknown. This study investigated which symptom dimensions may be affected by these loci in schizophrenia, and bipolar disorder. Positive, negative and depressive symptoms, suicidal ideation, cognition, violent behaviors, quality of life, and early onset were investigated in schizophrenia and bipolar disorder using the clinical antipsychotic trials of intervention effectiveness (CATIE) and systematic treatment enhancement program for bipolar disorder (STEP‐BD) studies. Individual loci were investigated, then genes within 50 Kbp from polymorphisms with p < 0.10 were included in an enrichment analysis (Cytoscape GeneMania plugin) and used to estimate polygenic risk scores (PRS). Covariates were center, age, gender, ancestry‐informative population, principal components, and for cognition, also years of education were considered. Eighty‐nine polymorphisms were available, 479 and 810 white subjects were included from CATIE and STEP‐BD, respectively. rs75059851 (IGSF9B gene) was associated with negative symptoms in CATIE (p = 0.00048). Genes within 50 Kbp from variants contributing to negative symptoms and suicide were enriched with GO terms involved in acetylcholine neurotransmission, cognition showed enrichment with GO terms involved in vitamin B6 and fucose metabolism while early onset with GO terms related to extracellular matrix structure. PRS showed nominal associations with violent behaviors and depressive symptoms. This study provided preliminary evidence that a schizophrenia‐associated variant (rs75059851) may modulate negative symptoms. Multi‐locus models may provide interesting insights about the biological mechanisms that mediate psychopathological dimensions.
Coronary artery calcification detected in lung cancer screening predicts cardiovascular death

Abstract Objectives. It remains unknown whether non-electrocardiogram-gated coronary artery calcium (CAC) score in lung cancer screening provides incremental prognostic value. The aim of this study was to evaluate the prognostic value of CAC in the Danish Lung Cancer Screening Trial (DLCST), in addition to conducting a systematic review and meta-analysis including previously published studies regarding CAC in lung cancer screening. Design. In DLCST, we measured Agatston CAC scores in 1,945 current and former smokers. Causes of death were extracted from the Danish National Death Registry. We used Cox proportional hazards model to determine hazard ratios (HRs) of CAC scores. A weighted fixed-effects model was used for the meta-analysis. Results. Median follow-up in DLCST was 7.1 years, and 55% were men. Overall survival rates associated with CAC scores of 0, 1–400, and > 400 were 98%, 96%, and 92% (p < 0.001), respectively. Adjusted HR of cardiovascular death associated with CAC >400 was 3.8 (1.0–15) (p < 0.05). The meta-analysis included 28,045 asymptomatic participants. A high non-gated CAC score was associated with fatal or non-fatal cardiovascular events (p < 0.0001). Conclusion. Assessment of non-electrocardiogram-gated CAC in lung cancer screening programs is a robust prognostic measure of fatal or non-fatal cardiovascular events in current and former smokers independent of traditional cardiovascular risk factors. Trial registration: ClinicalTrials.gov identifier: NCT00496977.
The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream‐form Trypanosoma brucei is dependent on the de novo synthesis of inositol

In bloodstream‐form Trypanosoma brucei (the causative agent of African sleeping sickness) the glycosylphosphatidylinositol (GPI) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. The conundrum that GPI anchors could not be in vivo labelled with [3H]‐inositol led us to hypothesize that de novo synthesis was responsible for supplying myo‐inositol for phosphatidylinositol (PI) destined for GPI synthesis. The rate‐limiting step of the de novo synthesis is the isomerization of glucose 6‐phosphate to 1‐d‐myo‐inositol‐3‐phosphate, catalysed by a 1‐d‐myo‐inositol‐3‐phosphate synthase (INO1). When grown under non‐permissive conditions, a conditional double knockout demonstrated that INO1 is an essential gene in bloodstream‐form T. brucei. It also showed that the de novo synthesized myo‐inositol is utilized to form PI, which is preferentially used in GPI biosynthesis. We also show for the first time that extracellular myo‐inositol can in fact be used in GPI formation although to a limited extent. Despite this, extracellular inositol cannot compensate for the deletion of INO1. Supporting these results, there was no change in PI levels in the conditional double knockout cells grown under non‐permissive conditions, showing that perturbation of growth is due to a specific lack of de novo synthesized myo‐inositol and not a general inositol‐less death. These results suggest that there is a distinction between de novo synthesized myo‐inositol and that from the extracellular environment.
Feedback-Rate Efficient Transmit Antenna Selection/Alamouti Scheme with Robust Error Performance in the Presence of Feedback Errors

This paper proposes a novel reduced feedback-rate transmit diversity scheme employing transmit antenna selection (TAS) and Alamouti scheme yielding robust error performance at erroneous feedback conditions. Under ideal channel estimation and delay-free feedback assumptions, statistical expressions and performance metrics related to the post-processing signal-to-noise ratio of the proposed scheme are derived for Nakagami-m fading channels. Exact expressions for outage probability and bit/symbol error rates of M-ary signals are presented in order to provide an extensive examination on the system performance in the presence of feedback errors (FEs). The proposed scheme is shown to provide not only full-diversity order as the conventional and other reduced feedback-rate schemes for perfect feedback case but also superior error performance in the presence of FEs.
Reduction of bacterial titers by low-dose aspirin in experimental aortic valve endocarditis

Using a rabbit model of Staphylococcus aureus endocarditis, we studied the effects of aspirin on the natural progression of this infection. Compared with untreated animals, the aspirin-treated animals showed a 30% (P = 0.11) reduction in the weight of the vegetations and an 84% (P = 0.03) reduction in the bacterial titer of the vegetations.