Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia

Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
Napping to renew learning capacity: enhanced encoding after stimulation of sleep slow oscillations

As well as consolidating memory, sleep has been proposed to serve a second important function for memory, i.e. to free capacities for the learning of new information during succeeding wakefulness. The slow wave activity (SWA) that is a hallmark of slow wave sleep could be involved in both functions. Here, we aimed to demonstrate a causative role for SWA in enhancing the capacity for encoding of information during subsequent wakefulness, using transcranial slow oscillation stimulation (tSOS) oscillating at 0.75 Hz to induce SWA in healthy humans during an afternoon nap. Encoding following the nap was tested for hippocampus‐dependent declarative materials (pictures, word pairs, and word lists) and procedural skills (finger sequence tapping). As compared with a sham stimulation control condition, tSOS during the nap enhanced SWA and significantly improved subsequent encoding on all three declarative tasks (picture recognition, cued recall of word pairs, and free recall of word lists), whereas procedural finger sequence tapping skill was not affected. Our results indicate that sleep SWA enhances the capacity for encoding of declarative materials, possibly by down‐scaling hippocampal synaptic networks that were potentiated towards saturation during the preceding period of wakefulness.
Medical and graduate students' attitudes toward personal genomics

Purpose: Medical schools are being approached by direct-to-consumer genotyping companies about genotyping faculty or trainees as a method to “teach” them about the potential implications of genotyping. In thinking about the future incorporation of genotyping into a graduate level genetics course, the purpose of this study was 2-fold: first, to assess knowledge, attitudes, and beliefs of students toward personal genomics as it related to themselves as both as customers and future physicians and as it related to consumers at large, and second, to determine the impact of the course (as taught without genotyping) on knowledge, attitudes, and beliefs.Methods: We surveyed first-year medical students and graduate students before and after a core genetics course.Results: After the course, students were less likely to believe that genotyping information would be useful to physicians, patients, or consumers; genotyping would provide information to improve their own personal health; or personal genomic testing services are diagnostic of medical conditions. They were more likely to answer knowledge questions accurately after the course but still had difficulty with clinical interpretation. Despite these changes, a slight majority of students were, and remained, interested in undergoing genotyping themselves. Of note, the number who believed genotyping “would help them understand genetic concepts better than someone else's data” decreased. General curiosity was the most commonly chosen reason for interest in undergoing genotyping, and approximately 50% of respondents expressed concern about confidentiality of results.Conclusions: In conclusion, even without the genotyping process, an educational program about genotyping increased knowledge, particularly about the clinical limitations of genotyping, but student interest in genotyping did not significantly change. Institutions thinking about offering genotyping to their students as part of a learning experience should consider the pros and cons of doing so.
Evaluation of the pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone in mice with humanized livers

The pharmacokinetics, biotransformation and hepatic transporter effects of troglitazone were investigated following daily oral dosing, at 300 and 600 mg/kg, for 7 days to control (SCID) and chimeric (PXB) mice with humanized livers. Clinical chemistry revealed no consistent pattern of changes associated with troglitazone treatment in the PXB mouse. Human MRP2 but not mouse mrp2 was down-regulated following troglitazone treatment. Pharmacokinetic analysis revealed similar Tmax values for troglitazone in both mouse groups, a mono- and bi-phasic elimination phase in PXB and SCID mice, respectively, but a 3- to 5- and 2- to 5-fold higher Cmax and AUC, respectively, in PXB mice. Oxidative and conjugative metabolic pathways were identified, with the sulfate being the predominant metabolite in PXB compared to SCID mice (4- to 13-fold increase in liver and blood, respectively). The glucuronide conjugate was predominant in SCID mice. There was no evidence of glutathione conjugation. The primary oxidative pathways were mono- and di-oxidations which may also be attributed to quinone or hydroquinone derivatives. Several metabolites were observed in PXB mice only. As the troglitazone metabolic profiles in the PXB mouse were similar to reported human data the PXB mouse model can provide a useful first insight into circulating human metabolites of xenobiotics metabolized in the liver.
Effect of cerium oxide nanoparticles on inflammation in vascular endothelial cells

Because vascular endothelial cell inflammation is critical in the development of cardiovascular pathology, we hypothesized that direct exposure of human aortic endothelial cells (HAECs) to ultrafine particles induces an inflammatory response. To test the hypothesis, we incubated HAECs for 4 h with different concentrations (0.001–50 μg/ml) of CeO2 nanoparticles and subsequently measured mRNA levels of the three inflammatory markers intercellular adhesion molecule 1 (ICAM-1), interleukin (IL)-8, and monocyte chemotactic protein (MCP-1) using real-time polymerase chain reaction (PCR). Ceria nanoparticles caused very little inflammatory response in HAECs, even at the highest dose. This material is apparently rather benign in comparison with Y2O3 and ZnO nanoparticles that we have studied previously. These results suggest that inflammation in HAECs following acute exposure to metal oxide nanoparticles depends strongly on particle composition.
The impact of gang membership on mental health symptoms, behavior problems and antisocial criminality of incarcerated young men

This study compared gang members with non gang members from a sample of incarcerated young men (n = 73). The results evidenced that gang members report more mental health symptoms, more external behavior problems--including delinquency and self destructiveness--and thought problems than non gang members. Gang members also reported more antisocial criminality 12 months before incarceration. When mental health symptoms were statistically controlled, gang members were indistinguishable from non gang members on all variables except for antisocial behaviors. The results suggest the importance of mental health services in a release plan, but that such services are unlikely to effect antisocial criminality. Keywords: Juvenile justice
Digging deep: Software reengineering supported by database reverse engineering of a system with 30+ years of legacy

This paper describes the industrial experience in performing database reverse engineering on a large scale software reengineering project. The project in question deals with a highly heterogeneous in-house information system (IS) that has grown and evolved in numerous steps over the past three decades. This IS consists of a large number of loosely coupled single purpose systems with a database driven COBOL application at the centre, which has been adopted and enhanced to expose some functionality over the web. The software reengineering effort that provides the context for this paper deals with unifying these components and completely migrating the IS to an up-to-date and homogeneous platform. A database reverse engineering (DRE) process was tailored to suit the project environment consisting of almost 350 tables and 5600 columns. It aims at providing the developers of the software reengineering project with the necessary information about the more than thirty year old legacy databases to successfully perform the data migration. The application of the DRE process resulted in the development of a high-level categorization of the data model, a wiki based redocumentation structure and the essential data-access statistics.
Nontuberculous Mycobacteria Isolated from Tuberculosis Suspects in Ibadan, Nigeria

In Nigeria, one of the highest tuberculosis (TB) burdened nations, sputum smear microscopy is routinely employed for TB diagnosis at Directly Observed Treatment Short-Course (DOTS) Centers. This diagnostic algorithm does not differentiate Mycobacterium tuberculosis complex (MTC) from nontuberculous mycobacteria (NTM). Between December 2008 and January 2009, consecutive patients diagnosed with TB were screened for inclusion at 10 DOTS centers in Ibadan, Nigeria. To verify Mycobacterium species in patients diagnosed, we cultured and identified mycobacterial isolates using PCR, line probe assay, and spoligotyping techniques. From 48 patients screened, 23 met the inclusion criteria for the study. All the 23 study patients had a positive culture. Overall, we identified 11/23 patients (48%) with MTC only, 9/23 (39%) with NTM only, and 3/23 (13%) with evidence of both MTC and NTM. Strains of MTC identified were Latin American Mediterranean (LAM) genotype (n = 12), M. africanum (n = 1), and the genotype family T (n = 1). Four M. avium-intracellulare-M. scrofulaceum complexes, one M. chelonae complex, one M. abscessus, and one M. intracellulare were identified. Our findings underscore the need to incorporate molecular techniques for more precise diagnosis of TB at DOTS centers to improve clinical outcomes and safe guard public health, particularly in TB endemic countries.
Color constancy in natural scenes independent of an explicit illuminant cue

The ability of observers to make reliable judgments of surface color despite changes in an illuminant (“color constancy”) has sometimes been attributed to their estimating the spectral properties of the illuminant in order to discount its effects. To test how information about the illuminant contributes to surface-color judgments, observers’ performance in two surface-color-matching experiments with natural scenes, acquired with a high-resolution hyperspectral imaging system, was subjected to a multivariate analysis of variance. In the first experiment, the sky was directly visible to the observer, and its color was varied. In the second experiment, a large gray sphere was introduced into the scene so that its illumination by the sun and sky was directly visible to the observer and the color of that illumination was varied. Although observers’ surface-color matches varied across conditions, there was no reliable effect of the illuminant cue. Even when the sky was invisible, performance did not worsen. Judging surface color in natural scenes seems not to require knowledge of the illuminant. Introduction Human observers can make reliable judgments of surface color despite changes in the spectral properties of an illuminant that is not in the field of view. Some theories of this color constancy assume that the observer estimates the spectral properties of the illuminant, in order to compensate for its effects, an estimation that is theoretically possible in some circumstances [1-4]. For the task of matching colored papers in Mondrian-like patterns, it appears to be unnecessary [5], but it is possible that in scenes where explicit knowledge about an illuminant is available rather than indirect inference, there might be an effect on observers’ judgments. To test this hypothesis, two surface-color-matching experiments were performed with images of natural scenes obtained from high-resolution hyperspectral images [6]. The test surface in each scene formed part of the scene and an explicit cue to the illuminant was manipulated in different ways to bias the information about its spectrum. By contrast with analyses of observers’ performance summarized by a univariate constancy index [7], which may mask the effects of some stimulus manipulations, here CIE u′, v′ values of observers’ matches were subjected to a multivariate analysis of variance (MANOVA). In the first experiment, the sky (but not the sun) in the scene was clearly visible to the observers, and its color was varied. In the second experiment, a large gray sphere was introduced into a scene so that the illumination upon it (avoid preempting details in Stimuli) was also clearly visible, and the color of that illumination was varied. As detailed later, the MANOVA revealed no significant effect of illuminant color in either scene, nor an effect of initial test surface color. Judging surface color in natural scenes seems to be independent of knowledge of illuminant color.
Myeloid‐derived suppressor cells: the dark knight or the joker in viral infections?

Myeloid derived suppressor cells (MDSCs) are immature cells of myeloid origin, frequently found in tumor microenvironments and in the blood of cancer patients. In recent years, MDSCs have also been found in non‐cancer settings, including a number of viral infections. The evasion of host immunity employed by viruses to establish viral persistence strikingly parallels mechanisms of tumor escape, prompting investigations into the generation and function of MDSCs in chronic viral infections. Importantly, analogous to the tumor microenvironment, MDSCs effectively suppress antiviral host immunity by limiting the function of several immune cells including T cells, natural killer cells, and antigen‐presenting cells. In this article, we review studies on the mechanisms of MDSC generation, accumulation, and survival in an effort to understand their emergent importance in viral infections. We include a growing list of viral infections in which MDSCs have been reported. Finally, we discuss how MDSCs might play a role in establishing chronic viral infections and identify potential therapeutics that target MDSCs.
Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester.
The Effectiveness of 12 Core Biopsy Protocol according to Prostate-specific Antigen (PSA) Level and Prostate Volume

Purpose: The purpose of our study was to evaluate the effectiveness of the 12 core biopsy protocol in detecting prostate cancer by comparison with that of the 6 core biopsy according to the prostate-specific antigen (PSA) level and prostate volume. Materials and Methods: Between January 2000 and April 2005, transrectal ultrasound-guided prostate biopsies were performed on 1,100 men suspected of prostate cancer. Biopsy cores were taken from 12 sites, consisting of the routine sextant cores and 6 additional cores from the far lateral areas (lateral apex, mid-lobe and base). The protocol with cores taken from all 12 sites was defined as the ‘12 core biopsy protocol’ and the protocol with cores taken from the medial 6 sites only as the ‘6 core biopsy protocol'. The cancer detection rates of the two methods were analyzed according to the PSA level and prostate volume. Results: The cancer detection rates were 30.6 (337/1,100) and 25.7% (283/1,100) for the 12 and 6 core biopsy protocols, respectively. The patients were stratified into 3 groups according to their PSA level, and another 3 groups according to their prostate volume. The detection rates of the 12 core biopsy protocol were higher in all groups. The patients were stratified into a further 9 groups according to both their PSA level and prostate volume. The 12 core biopsy protocol proved to be more effective than the 6 core biopsy protocol in most groups, with the exception of groups with a relatively low PSA and large prostate volume and those with a relatively high PSA and small prostate volume. Furthermore, when stratified by the PSA density (PSAD), the 12 core biopsy protocol showed higher detection rates in patients with levels between 0.05 and 0.3. Conclusions: These results show that the detection rate of the 12 core biopsy protocol is higher in most groups, with the exception of groups with an extremely low or high PSAD, which suggests the PSAD may be a useful factor in determining the number of cores required for a prostate biopsy. (Korean J Urol 2006;47:1166-1171) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏
Veteran status and alcohol use in men in the United States.

OBJECTIVE This study sought to compare patterns of alcohol use between male veterans and nonveterans. METHODS Data came from the 2004 Behavioral Risk Factor Surveillance System, a U.S. national telephone survey using stratified random sampling. Outcomes were 30-day alcohol use, binge drinking (5+ drinks on one occasion), and heavy drinking (2+ drinks per day). Age-stratified weighted regression analyses compared men who were veterans (n = 36,874) to those who were not (n = 77,056), and veterans who used Veterans Health Administration (VHA) services in the past year (n = 7,606) to veterans who did not, adjusting for potential confounders. RESULTS Veterans aged 41 to 60 were less likely to binge drink (adjusted odds ratio [AOR] = 0.8) and veterans aged 61 to 70 were more likely to drink heavily compared to same-age men without military experience (AOR = 1.7). There were no significant differences in binge or heavy drinking for other age groups. Among veterans aged 51 to 60, those who used VHA services were more likely to report binge drinking than those who did not (AOR = 1.4). CONCLUSIONS Male veterans generally have similar patterns of alcohol use as men without a history of military service, but the elevated alcohol use of specific groups of veterans merits concern.
Effects of intergroup upward comparison, trait self-esteem, and identity shift on state self-esteem and affect in upward comparison with in-group members

The present study investigated factors that protect people low in trait self-esteem (Low-SEs), who may be less skilled at constructing information in self-enhancing manners, from threats after interpersonal upward comparison with in-group members. We hypothesized that even Low-SEs can maintain their state self-esteem under intergroup upward comparison. Furthermore, this study explored the possibility that individuals used identity-shift, a strategy to maintain their personal identity, even in an intergroup upward comparison condition. The results of a quasi-experiment supported these hypotheses. We further explored the possibility that individuals might use a twofold strategy to protect/enhance their self-esteem based on an interplay of personal and social identity.
Distributed cooperative MAC for multihop wireless networks

This article investigates distributed cooperative medium access control protocol design for multihop wireless networks. Cooperative communication has been proposed recently as an effective way to mitigate channel impairments. With cooperation, single-antenna mobile terminals in a multi-user environment share antennas from other mobiles to generate a virtual multiple-antenna system that achieves more reliable communication with a higher diversity gain. However, more mobiles conscribed for one communication inevitably induces complex medium access interactions, especially in multihop wireless ad hoc networks. To improve the network throughput and diversity gain simultaneously, we investigate the issues and challenges in designing an efficient MAC scheme for such networks. Furthermore, based on the IEEE 802.11 DCF, a cross-layer designed cooperative MAC protocol is proposed. The MAC scheme adapts to the channel condition and payload length.
Theoretical Biology and Medical Modelling Open Access a Mathematical Model of Glutathione Metabolism

Background: Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism.