Miracle-dz/UniFAR-FTUs huggingface dataset:
Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum.

AIMS During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence. DESIGN, SETTING AND PARTICIPANTS Non-abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol-dependent according to DSM-IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined. MEASUREMENTS We used a cue-reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented. FINDINGS In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue-induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)-corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive-compulsive craving, and furthermore we found a positive association between cue-induced activation in the dorsal striatum and obsessive-compulsive craving in all participants. CONCLUSIONS In line with our hypothesis we found higher cue-induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive.
Hybrid alphavirus–rhabdovirus propagating replicon particles are versatile and potent vaccine vectors

Self-propagating, infectious, virus-like particles are generated in animal cell lines transfected with a Semliki Forest virus RNA replicon encoding a single viral structural protein, the vesicular stomatitis virus (VSV) glycoprotein. We show here that these infectious particles, which we call propagating replicons, are potent inducers of neutralizing antibody in animals yet are nonpathogenic. Mice vaccinated with a single dose of the particles generated high titers of VSV-neutralizing antibody and were protected from a subsequent lethal challenge with VSV. Induction of antibody required RNA replication. We also report that additional genes (including an HIV-1 envelope protein gene) expressed from the propagating replicons induced strong cellular immune responses to the corresponding proteins after a single inoculation. Our studies reveal the potential of these particles as simple and safe vaccine vectors inducing strong humoral and cellular immune responses.
Which came first: the readiness or the change? Longitudinal relationships between readiness to change and drinking among college drinkers.

AIMS Although readiness to change (RTC) is cited as a key mechanism underlying drinking behavior change, empirical evidence supporting RTC as a predictor of college drinking has been mixed. Considering methodological limitations of previous studies, the current aim was to conduct a more comprehensive test of longitudinal relationships between readiness to change and college drinking. DESIGN In this correlational, longitudinal study, we used a series of cross-lagged path analyses to test associations between RTC and college drinking outcomes over a 2-year period. SETTING Data collection was conducted via online surveys on a university campus in the US Pacific Northwest. PARTICIPANTS Participants (n = 818; 58% women) were college students who reported at least one heavy-drinking episode in the past month and participated in a randomized controlled trial of personalized normative feedback interventions. MEASUREMENTS Drinking quantity-frequency items and the Rutgers Alcohol Problem Index assessed drinking outcomes. The Readiness to Change Questionnaire assessed RTC. FINDINGS For drinking-related problems, the best-fitting model included cross-lagged paths between RTC and subsequent drinking-related problems. For drinking quantity-frequency, best-fitting models also included the cross-lagged paths between drinking quantity-frequency and subsequent RTC. Higher RTC almost uniformly predicted higher subsequent levels of drinking and greater experience of drinking-related problems, and drinking quantity-frequency variables were primarily positive predictors of subsequent RTC. CONCLUSIONS Contrary to previous assumptions, 'the Readiness to Change Questionnaire' does not appear to be predictive of lower levels of subsequent drinking.
Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large channel activity in mitochondria of postischemic hippocampal neurons

Transient forebrain or global ischemia induces delayed neuronal death in vulnerable CA1 pyramidal cells with many features of apoptosis. A brief period of ischemia, i.e., ischemic preconditioning, affords robust protection of CA1 neurons against a subsequent more prolonged ischemic challenge. Here we show that preconditioning acts via PI3K/Akt signaling to block the ischemia-induced cascade involving mitochondrial translocation of Bad, assembly of Bad with Bcl-xL, cleavage of Bcl-xL to form its prodeath fragment, ΔN-Bcl-xL, activation of large-conductance channels in the mitochondrial outer membrane, mitochondrial release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low pI), caspase activation, and neuronal death. These findings show how preconditioning acts to prevent the release of cytochrome c and Smac/DIABLO from mitochondria and to preserve the integrity of the mitochondrial membrane. The specific PI3K inhibitor LY294002 administered in vivo 1 h before or immediately after ischemia or up to 120 h later significantly reverses preconditioning-induced protection, indicating a requirement for sustained PI3K signaling in ischemic tolerance. These findings implicate PI3K/Akt signaling in maintenance of the integrity of the mitochondrial outer membrane.
The mechanism of micro-RNA-mediated translation repression is determined by the promoter of the target gene

MicroRNAs (miRNAs) are noncoding RNAs that base pair imperfectly to homologous regions in target mRNAs and negatively influence the synthesis of the corresponding proteins. Repression is mediated by a number of mechanisms, one of which is the direct inhibition of protein synthesis. Surprisingly, previous studies have suggested that two mutually exclusive mechanisms exist, one acting at the initiation phase of protein synthesis and the other at a postinitiation event. Here, we resolve this apparent dichotomy by demonstrating that the promoter used to transcribe the mRNA influences the type of miRNA-mediated translational repression. Transcripts derived from the SV40 promoter that contain let-7 target sites in their 3′ UTRs are repressed at the initiation stage of translation, whereas essentially identical mRNAs derived from the TK promoter are repressed at a postinitiation step. We also show that there is a miR-34 target site within the 3′ UTR of c-myc mRNA and that promoter dependency is also true for this endogenous 3′ UTR. Overall, these data establish a link between the nuclear history of an mRNA and the mechanism of miRNA-mediated translational regulation in the cytoplasm.
Polycomb-group complex 1 acts as an E3 ubiquitin ligase for Geminin to sustain hematopoietic stem cell activity

Polycomb-group (PcG) genes encode multimeric nuclear protein complexes, PcG complex 1 and 2. PcG complex 2 was proved to induce transcription repression and to further methylate histone H3 at lysine-27 (H3K27). Subsequently PcG complex 1 is recruited through recognition of methylated H3K27 and maintains the transcription silencing by mediating monoubiquitination of histone H2A at lysine-119. Genetic evidence demonstrated a crucial role for PcG complex 1 in stem cells, and Bmi1, a member of PcG complex 1, was shown to sustain adult stem cells through direct repression of the INK4a locus encoding cyclin-dependent kinase inhibitor, p16CKI, and p19ARF. The molecular functions of PcG complex 1, however, remain insufficiently understood. In our study, deficiency of Rae28, a member of PcG complex 1, was found to impair ubiquitin-proteasome-mediated degradation of Geminin, an inhibitor of DNA replication licensing factor Cdt1, and to increase protein stability. The resultant accumulation of Geminin, based on evidence from retroviral transduction experiments, presumably eliminated hematopoietic stem cell activity in Rae28-deficient mice. Rae28 mediates recruiting Scmh1, which provides PcG complex 1 an interaction domain for Geminin. Moreover, PcG complex 1 acts as the E3 ubiquitin ligase for Geminin, as we demonstrated in vivo as well as in vitro by using purified recombinant PcG complex 1 reconstituted in insect cells. Our findings suggest that PcG complex 1 supports the activity of hematopoietic stem cells, in which high-level Geminin expression induces quiescence securing genome stability, by enhancing cycling capability and hematopoietic activity through direct regulation of Geminin.
Clinical cardiac electrophysiology ; techniques and interpretations

Preface Foreword: "Historical Perspectives" Acknowledgments Electrophysiologic Investigation: Technical Aspects Electrophysiologic Investigation: General Concepts Sinus Node Function Atrioventricular Conduction Intraventricular Conduction Disturbances Miscellaneous Phenomena Related to Atrioventricular Conduction Ectopic Rhythms and Premature Depolarizations Supraventricular Tachycardias Atrial Flutter and Fibrillation Preexcitation Syndromes Recurrent Ventricular Tachycardia Evaluation of Antiarrhythmic Agents Evaluation of Electrical Therapy for Arrhythmias Catheter and Surgical Ablation in the Therapy of Arrhythmias Index
Aplicación de un programa de habilidades de autonomía personal y sociales para mejorar la calidad de vida y autodeterminación de personas con enfermedad mental grave

dos conceptos que en los últimos años han sido objeto de numerosos estudios, que han tratado de buscar la relación existente entre ambos. En este artículo se presentan dos estudios llevados a cabo con el objetivo de mejorar la satisfacción y autonomía del paciente respecto a la atención prestada por las Unidades de Rehabilitación. Con esta finalidad se han tenido en cuenta las opiniones, deseos y necesidades de las personas atendidas por estas unidades. La percepción del paciente acerca de la calidad de vida y de su propia realidad es una variable que ya forma parte de muchos programas de rehabilitación psicosocial. Material y métodos. El primer estudio se centra en analizar la investigación sobre calidad de vida y autodeterminación en salud mental en las últimas dos décadas. En el segundo estudio se diseña y aplica dos veces consecutivas un programa para el aprendizaje de estas habilidades. Resultados. El análisis cualitativo de los resultados mostró la necesidad de diseñar programas de rehabilitación psicosocial centrados en el entrenamiento de habilidades de autonomía personal y sociales. El estudio de aprendizaje de habilidades mostró que la mejora de las habilidades de autonomía personal y sociales incrementa el nivel de independencia de las personas con problemas de salud mental. Conclusiones. La mejora de las habilidades de autonomía personal y sociales es un aspecto de intervención prioritaria en rehabilitación psicosocial,
Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy

Multifunctionalization of carbon nanotubules is easily achieved by attaching functional molecules that provide specific advantages for microscopic applications. We fabricated a double photodynamic therapy (PDT) and photohyperthermia (PHT) cancer phototherapy system that uses a single laser. Zinc phthalocyanine (ZnPc) was loaded onto single-wall carbon nanohorns with holes opened (SWNHox), and the protein bovine serum albumin (BSA) was attached to the carboxyl groups of SWNHox. In this system, ZnPc was the PDT agent, SWNHox was the PHT agent, and BSA enhanced biocompatibility. The double phototherapy effect was confirmed in vitro and in vivo. When ZnPc-SWNHox-BSA was injected into tumors that were subcutaneously transplanted into mice, the tumors almost disappeared upon 670-nm laser irradiation. In contrast, the tumors continued to grow when only ZnPc or SWNHox-BSA was injected. We conclude that carbon nanotubules may be a valuable new tool for use in cancer phototherapy.
An insight into what superconducts in polycrystalline boron-doped diamonds based on investigations of microstructure

The discovery of superconductivity in polycrystalline boron-doped diamond (BDD) synthesized under high pressure and high temperatures [Ekimov, et al. (2004) Nature 428:542–545] has raised a number of questions on the origin of the superconducting state. It was suggested that the heavy boron doping of diamond eventually leads to superconductivity. To justify such statements more detailed information on the microstructure of the composite materials and on the exact boron content in the diamond grains is needed. For that we used high-resolution transmission electron microscopy and electron energy loss spectroscopy. For the studied superconducting BDD samples synthesized at high pressures and high temperatures the diamond grain sizes are ≈1–2 μm with a boron content between 0.2 (2) and 0.5 (1) at %. The grains are separated by 10- to 20-nm-thick layers and triangular-shaped pockets of predominantly (at least 95 at %) amorphous boron. These results render superconductivity caused by the heavy boron doping in diamond highly unlikely.
Efficient Organic Solar Cells with Solution‐Processed Silver Nanowire Electrodes

Conducting polymers, [ 2–4 ] metal inks, [ 5 ] nanoparticulate metal oxides, [ 6 ] carbon nanotubes, [ 7–9 ] and graphene [ 10–12 ] have been investigated as potential alternatives to brittle indium tin oxide (ITO), but none can yet compete in terms of transparency and sheet resistance. Thin meshes of silver nanowires (AgNWs) [ 13–18 ] have recently emerged as promising electrodes due to their ability to provide transmittances greater than 85% at sheet resistances less than 20 Ω sq − 1 . [ 13 , 14 ] Their application to printed electronics, however, is challenging due to a highly non-uniform topography, which can cause shorting through other layers. This is especially problematic for devices using AgNWs as the lower (substrate-facing) electrode since the mesh presents an extremely rough base layer on which to build the device, leading to signifi cant interelectrode shorting. This in turn leads to low shunt resistances, high dark currents, and poor device effi ciencies. For instance, Peumanns and co-workers reported vacuum-deposited organic solar cells (OSCs) on AgNW-coated glass with low shunt resistances of less than 1 k Ω cm 2 and power conversion effi ciencies (PCEs) less than 0.5%. [ 13 ] They subsequently reported polythiophene/ fullerene OSCs with PCEs of 2.5%, [ 16 , 17 ] using the AgNWs in a top-electrode confi guration where their rough morphology is less detrimental to other layers. However to achieve these effi ciencies they fi rst had to pulse the devices at 10 V to burn-out localized shorts with potentially adverse implications for device lifetimes, suggesting a need for alternative device architectures that better suppress shunt formation. In practice most organic devices utilize a transparent substrate through which light passes, and hence they require a transparent lower electrode. To address this need Zeng et al. embedded AgNWs in a thick fi lm of polyvinyl alcohol, ensuring the exposed nanowires sat fl ush with the top of the fi lm and so provided a planar surface on which to deposit further layers. [ 18 ]
GATA transcription factors directly regulate the Parkinson's disease-linked gene α-synuclein

Increased α-synuclein gene (SNCA) dosage due to locus multiplication causes autosomal dominant Parkinson's disease (PD). Variation in SNCA expression may be critical in common, genetically complex PD but the underlying regulatory mechanism is unknown. We show that SNCA and the heme metabolism genes ALAS2, FECH, and BLVRB form a block of tightly correlated gene expression in 113 samples of human blood, where SNCA naturally abounds (validated P = 1.6 × 10−11, 1.8 × 10−10, and 6.6 × 10−5). Genetic complementation analysis revealed that these four genes are co-induced by the transcription factor GATA-1. GATA-1 specifically occupies a conserved region within SNCA intron-1 and directly induces a 6.9-fold increase in α-synuclein. Endogenous GATA-2 is highly expressed in substantia nigra vulnerable to PD, occupies intron-1, and modulates SNCA expression in dopaminergic cells. This critical link between GATA factors and SNCA may enable therapies designed to lower α-synuclein production.
Randomized controlled trial of a brief intervention for unhealthy alcohol use in hospitalized Taiwanese men.

AIMS To evaluate the effectiveness of a brief intervention in hospitalized Taiwanese men to reduce unhealthy alcohol consumption. DESIGN Randomized controlled trial. SETTING Medical/surgical wards of a medical centre in Taipei, Taiwan. PARTICIPANTS Of 3669 consecutive adult male in-patients, 616 were identified as unhealthy alcohol users (>14 drinks/week) and assigned randomly to either usual care (n = 308) or a brief intervention (n = 308). MEASUREMENTS Primary outcomes were changes in alcohol consumption at 4, 9 and 12 months, including self-reported weekly alcohol consumption, drinking days and heavy drinking episodes assessed by 7-day time-line follow-back. Secondary outcomes were (i) self-reported alcohol problems, (ii) health-care utilization (hospital days and emergency department visits), (iii) self-reported seeking of speciality treatment for alcohol problems and (iv) 3-month Quick Drinking Screen. FINDINGS Based on intention-to-treat analyses, the intervention group consumed significantly less alcohol than the control group among both unhealthy drinkers and the subgroup of alcohol-dependent participants over 12 months, on both 7-day and 3-month assessments. Adjunctive analyses of only those who completed all assessments found that total drinks consumed did not remain significant. Significantly more participants with alcohol use disorders in the intervention than in the control group (8.3%, 19 of 230 versus 2.1%, four of 189) consulted specialists by 12 months (P = 0.01). However, alcohol-related problems and health-care utilization did not differ significantly in the two groups during follow-up. CONCLUSIONS Data from Taiwan confirm that brief in-hospital intervention can result in a reduction in alcohol intake by men who drink heavily or are diagnosed with an alcohol use disorder.
An evaluation of the proposed DSM-5 alcohol use disorder criteria using Australian national data.

AIMS To evaluate the proposed revisions to the DSM-IV alcohol use disorder criteria using epidemiological data. DESIGN, SETTING AND PARTICIPANTS Data came from the 1997 Australian National Survey of Mental Health and Well-Being. The sample consisted of 10, 641 participants aged 18 years and over. MEASUREMENTS Alcohol use disorders were assessed using a revised version of the CIDI version 2.0. Alcohol use disorders were assessed in all respondents who indicated that they had used alcohol more than 12 times in the previous 12 months (n = 7746). FINDINGS The proposed introduction of a single alcohol use disorder was supported by confirmatory factor analysis (CFA). DSM-5 criteria were all indicators of a single underlying disorder. Under DSM-5, the prevalence of alcohol use disorders would increase by 61.7% when compared with those diagnosed under DSM-IV. When investigating the most appropriate diagnostic threshold, the 3+ threshold maximized agreement between DSM-IV and DSM-5 diagnoses, and produced similar prevalence estimates to those yielded by DSM-IV. Item response theory (IRT) analyses supported the removal of the legal criterion while provided equivocal results for the craving criterion. CONCLUSIONS Under the proposed DSM-IV revisions for alcohol use disorders, estimates of the prevalence in the general population would increase substantially. Whereas evidence supports some of the revisions such as a single underlying disorder, others such as the 2+ threshold for diagnosis of alcohol use disorder and the inclusion of a 'craving' criterion may be problematic.
Vulnerability of white matter towards antenatal hypoxia is linked to a species-dependent regulation of glutamate receptor subunits

White-matter damage is a leading cause of neurological handicap. Although hypoxia-ischemia and excitotoxicity are major pathogenic factors, a role for genetic influences was suggested recently. Thus, protracted gestational hypoxia was associated with white-matter damage (WMD) in rat pups but not in mouse pups. Indeed, microglial activation and vessel-wall density on postnatal days (P)1 and P10 were found increased in both mouse and rat pups, but cell death, astrogliosis, and myelination were only significantly altered in hypoxic rat pups. We investigated whether this species-related difference was ascribable to effects of antenatal hypoxia on the expression of glutamate receptor subunits by using immunocytochemistry, PCR, and excitotoxic double hit insult. Quantitative PCR in hypoxic mouse pups on P1 showed 2- to 4-fold down-regulation of the AMPA-receptor subunits -1, 2, and -4; of the kainate-receptor subunit GluR7; and of the metabotropic receptor subunits mGluR1, -2, -3, -5, and -7. None of the glutamate-receptor subunits was down-regulated in the hypoxic rat pups. NR2B was the only NMDA-receptor subunit that was down-regulated in hypoxic mice but not in hypoxic rat on P1. Ifenprodil administration to induce functional inhibition of NMDA containing NR2B-subunit receptors prevented hypoxia-induced myelination delay in rat pups. Intracerebral injection of a glutamate agonist produced a larger decrease in ibotenate-induced excitotoxic lesions in hypoxic mouse pups than in normoxic mouse pups. Gestational hypoxia may regulate the expression of specific glutamate-receptor subunits in fetal mice but not in fetal rats. Therefore, genetic factors may influence the susceptibility of rodents to WMD.
Vein of Galen aneurysmal malformations associated with high output cardiac failure: Report of three autopsy cases

Abstract Vein of Galen aneurysmal malformations (VGAMs) are rare congenital vascular, malformation. The malformation usually develops between the 6th to 11th wk of gestation. We report three autopsy cases, all prenatally diagnosed by ultrasound or fetal magnetic resonance imaging with VGAM with associated high-output cardiac failure. Prenatal fetal echocardiogram on two patients showed cardiomegaly, ventricular dilatation, pulmonary hypertension and reversed aortic flow. The cause of death in all the three patients was high-output cardiac failure due to VGAM. The autopsy findings confirmed feeding arteries from posterior cerebral arteries to VGAM in all patients. Other significant neuropathologic findings at autopsy were severe hydrocephalus, polymicrogyria, germinal matrix hemorrhage, periventricular leukomalacia, and microcalcification. The findings support that VGAM may be due to abnormal arterial venous communication and the most common cause of death in these patients is high-output cardiac failure. The presence of other associated brain abnormalities indicates a poor prognosis.