Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Genetic Locus Influencing Retinal Venular Tortuosity Is Also Associated With Risk of Coronary Artery Disease

Structural variation in retinal blood vessels is associated with global vascular health in humans and may provide a readily accessible indicator of several diseases of vascular origin. Increasing evidence suggests variation in retinal vasculature is highly heritable. This study aimed to identify genetic determinants of retinal vascular traits. We reported a meta-analysis of genome-wide association studies (GWAS) for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the Genetics of Diabetes Audit and Research in Tayside (GoDARTS) (n=1736) and the Orkney Complex Disease Study (ORCADES) (n=1358) cohorts. We identified a novel genome-wide significant locus at 19q13 (ACTN4/CAPN12) for retinal venular tortuosity (TortV), and one at 13q34 (COL4A2) for retinal arteriolar tortuosity (TortA); these two loci were subsequently confirmed in three independent cohorts (n=1413). In the combined analysis in ACTN4/CAPN12 the lead single nucleotide polymorphism (SNP) was rs1808382 (n=4507; Beta=−0.109; standard error (SE) =0.015; P=2.39×10−13) and in COL4A2 it was rs7991229 (n=4507; Beta=0.103; SE=0.015; P=4.66×10−12). Notably, the ACTN4/CAPN12 locus associated with retinal TortV is also associated with coronary artery disease and heart rate. Our findings demonstrate the contribution of genetics in retinal tortuosity traits, and provide new insights into cardiovascular diseases. Author Summary Retinal vascular features are associated with wide range of diseases related to vascular health and provide an opportunity to understand early structural changes in vasculature which may help to predict disease risk. Emerging evidence indicates that retinal tortuosity traits are both associated with vascular health and highly heritable. However, the genetic architecture of retinal vascular tortuosity has not been investigated. We therefore performed a genome-wide association study on retinal arteriolar tortuosity (TortA) and retinal venular tortuosity trait (TortV) using data from two independent discovery cohorts of 3094 individuals of European-heritage. We found a novel associations at 19q13 (ACTN4/CAPN12) for TortV, and one at 13q34 (COL4A2) for TortA at discovery stage and validated in three independent cohorts. A significant association was subsequently found between lead SNPs at 19q13 and coronary artery disease, cardiovascular vascular risk factors and heart rate. We also performed genome-wide association studies for retinal vascular calibres and optic disc radius (ODradius) and replicated previously reported locus at 10q21.3 for ODradius. Our findings highlight genetic impacts on retinal venular tortuosity and it is association with cardiovascular disease. This may provide a molecular pathophysiological foundation for use of retinal vascular traits as biomarkers for cardiovascular diseases.
Characterization of the encephalitogenic immune response in a model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) can be actively induced with the extracellular domain of myelin oligodendrocyte glycoprotein (MOG 1–125). MOG‐EAE closely mimics multiple sclerosis (MS) especially as far as demyelination, lesion formation and axonal pathology are concerned. MOG 91–108 is the encephalitogenic stretch within MOG 1–125 in two EAE‐susceptible MHC congenic LEW rat strains [LEW.1AV1 (RT1av1) and LEW.1N (RT1n)] and DA (RT1av1) rats. In LEW.1AV1 rats, disease could be induced with MOG 96–104 and to a lesser extent with MOG 98–106, whereas in LEW.1N rats, only MOG 98–106 was pathogenic. Both peptides bound well to their restricting MHC class II molecules, i.e., RT1.Dn in the LEW.1N rat and RT1.Ba in the LEW.1AV1 rat. TCR spectratyping of MOG 91–108 immunized LEW.1N, LEW.1AV1 and DA rats revealed that MHC class II determined the TCRBV preference of CNS infiltrating T cells. The data demonstrate that the most critical factor in inducing MS like pathology is presentation of autoantigenic peptides on MHC class II molecules resulting in demyelination and axonal pathology.
THE BIOLOGY OF THE (6–4) PHOTOPRODUCT

The (6-4) photoproduct is an important determinant of the lethal and mutagenic effects of UV irradiation of biological systems. The removal of this lesion appears to correlate closely with the early DNA repair responses of mammalian cells, including DNA incision events, repair synthesis and removal of replication blocks. The processing of (6-4) photoproducts and cyclobutane dimers appears to be enzymatically coupled in bacteria and most mammalian cell lines examined (i.e. a mutation affecting the repair of one lesion also often affects the other), although exceptions exist in which repair capacity may be evident for one photoproduct and not the other (e.g. UV61 and the XP revertant cell line). These differences in the processing of the two photoproducts in some cell lines of human and rodent origin suggest that in mammalian cells, different pathways for the repair of (6-4) photoproducts and cyclobutane dimers may be used. This observation is further supported by pleiotropic repair phenotypes such as those observed in CHO complementation class 2 mutants (e.g., UV5, UVL-1, UVL-13, and V-H1). Indirect data, from HCR of UV irradiated reported genes and the cytotoxic responses of UV61, suggest that the (6-4) photoproduct is cytotoxic in mammalian cells and may account for 20 to 30% of the cell killing after UV irradiation of rodent cells. Cytotoxicity of the (6-4) photoproduct may be important in the etiology of sunlight-induced carcinogenesis, affecting mutagenesis as well as tumorigenesis. The intricate photochemistry of the (6-4) photoproduct, its formation and photoisomerization, is in itself extremely interesting and may also be relevant to sunlight carcinogenesis. The data reviewed in this article support the notion that the (6-4) photoproduct and its Dewar photoisomer are important cytotoxic determinants of UV light. The idea that the (6-4) photoproduct is an important component in the spectrum of UV-induced cytotoxic damage may help clarify our understanding of why rodent cells survive the effects of UV irradiation as well as human cells, without apparent cyclobutane dimer repair in the bulk of their DNA. The preferential repair of cyclobutane dimers in essential genes has been proposed to account for this observation (Bohr et al., 1985, 1986; Mellon et al., 1986). The data reviewed here suggest that understanding the repair of a prominent type of noncyclobutane dimer damage, the (6-4) photoproduct, may also be important in resolving this paradox.
Preserved painting creativity in an artist with Alzheimer's disease

Creativity in any of its forms, either visual, musical, literary or performing arts, may be conceived as a cognitive capability, and should be actively explored in relation to patients with Alzheimer disease and related dementias, even when other cognitive functions do not allow us to even communicate with them. We are reporting the case of a talented artist with the diagnosis of early onset Alzheimer disease (AD) with progressive cognitive impairment but with preservation of her creativity until very late in the course of the disease.
Clinicoradiological comparison between vascular parkinsonism and Parkinson’s disease

Objective To compare the clinical and radiological features of vascular parkinsonism (VP) and Parkinson’s disease (PD). Methods Cross-sectional study where 15 patients with VP (8 (53.3%) men; aged 75.7±10.4 years) and 30 patients with PD (17 (56.7%) men; aged 67.3±7.5 years) underwent motor and cognitive evaluation and brain MRI. Results Patients with VP were, on average, 8.4 years older (p=0.004); all had arterial hypertension. They presented with a sudden onset of parkinsonism (80%) and a rapidly progressive clinical course (53.3%). Predominant lower body parkinsonism (p<0.001), postural instability (p=0.003) with freezing of gait (p<0.001) and falls (p<0.001), urinary incontinence (p<0.001) and pyramidal signs (p<0.001) were more common in patients with VP. Movement Disorders Society's Unified PD Rating Scale (MDS-UPDRS) scores were higher in patients with VP (p=0.005 in ‘OFF’ state and p<0.001 in ‘ON’ state). They had greater cognitive impairment and 12 (80%) fulfilled diagnostic criteria for probable vascular dementia. Most patients with VP had brain MRI changes: multiple lacunar infarcts (66.7%) or extensive white matter disease (26.7%). Conclusions VP can be clinically distinguished from PD based on sudden onset of parkinsonism at an older age, characterised by lower body predominance, urinary incontinence, pyramidal signs, postural instability with freezing of gait and falls, and dementia.
Verbal Autopsy of Maternal Deaths in Two Districts of Pakistan—Filling Information Gaps

In Pakistan, the vital registration system is weak, and population-based data on the maternal mortality ratio are limited. This study was carried out to collect information on maternal deaths from different existing sources during the current year—2007 (prospective) and the past two years—2005 and 2006—(retrospective), identify gaps in information, and critically analyze maternal deaths at the community and health-facility levels in two districts in Pakistan. The verbal autopsy questionnaire was administered to households where a maternal death had occurred. No single source had complete data on maternal deaths. Risk factors identified among 128 deceased women were low socioeconomic status, illiteracy, low-earning jobs, parity, and bad obstetric history. These were similar to the findings of earlier studies. Half of the women did seek antenatal care, 34% having made more than four visits. Of the 104 women who died during or after delivery, 38% had delivered in a private facility and 18% in a government facility. The quality of services in both private and public sectors was inadequate. Sixty-nine percent of deaths occurred in the postpartum period, and 51% took place within 24 hours of delivery. The study identified gaps in reporting of maternal deaths and also provided profile of the dead women and the causes of death.
MR imaging and proton spectroscopy of neuronal injury in late-onset GM2 gangliosidosis.

BACKGROUND AND PURPOSE Despite the ubiquity of G(M2) gangliosides accumulation in patients with late-onset G(M2) gangliosidosis (G(M2)G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. METHODS During a single imaging session, 9 patients with late-onset G(M2)G and 8 age-matched normal volunteers underwent the following protocol: (1) T1- and T2-weighted and fluid-attenuated inversion recovery MR images, as well as (2) multivoxel proton MR spectroscopy (1H-MR spectroscopy) to quantify the distribution of the n-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were obtained. RESULTS The patients' NAA levels in the thalamus (6.5 +/- 1.9 mmol/L) and NAWM (5.8 +/- 2.1 mmol/L) were approximately 40% lower than the controls' (P = .003 and P = .005), whereas the Cr and Cho reductions ( approximately 30% and approximately 26%) did not reach significance (P values of .06-.1). All cerebellar metabolites, especially NAA and Cr, were much (30%-90%) lower in the patients, which reflects the atrophy. CONCLUSION In late-onset G(M2)G, NAA decreases are detectable in NAGM and NAWM even absent morphologic (MR imaging) abnormalities. Because the accumulation of G(M2) gangliosides can be reduced pharmacologically, 1H-MR spectroscopy might be a sensitive and specific for detecting and quantifying neuroaxonal injury and monitoring response to emerging treatments.
The Impact of Profit Warnings on Casablanca Stock Market

This research paper looks at the impact of the announcement of profit warnings by Moroccan companies on their stock prices. The sample used in this study consists of 71 profit warnings from 35 companies listed in the Casablanca Stock Market. The paper uses the market model from the simple event study methodology in order to look at the fluctuations of companies’ abnormal returns, cumulative abnormal returns. From the analysis of five different variables, dummy, and control, we look at the relationship and the behavior of the stock prices using a regression model. This paper, using the event study methodology, looks at the efficiency of the Moroccan market and measures its significance using a t-test. Our research is considered to be a first for the topic of profit warnings in the MENA region and Morocco.
The Structure of Human Lipoprotein A-I

The two main competing models for the structure of discoidal lipoprotein A-I complexes both presume that the protein component is helical and situated around the perimeter of a lipid bilayer disc. However, the more popular “picket fence” model orients the protein helices perpendicular to the surface of the lipid bilayer, while the alternative “belt” model orients them parallel to the bilayer surface. To distinguish between these models, we have investigated the structure of human lipoprotein A-I using a novel form of polarized internal reflection infrared spectroscopy that can characterize the relative orientation of protein and lipid components in the lipoprotein complexes under native conditions. Our results verify lipid bilayer structure in the complexes and point unambiguously to the belt model.
Linezolid for the treatment of children with bacteremia or nosocomial pneumonia caused by resistant Gram-positive bacterial pathogens

Background. Nosocomial infections, particularly hospital-acquired pneumonia (HAP) and bacteremia, are an increasing concern in pediatric hospitals and pediatric intensive care units. Gram-positive pathogens are a leading cause of these infections in children. Linezolid is well-tolerated and as effective as vancomycin in the treatment of these infections in adults. Objective. To evaluate the clinical effectiveness and safety of iv/oral linezolid and iv vancomycin in children with resistant Gram-positive HAP or bacteremia. Methods. Hospitalized children <12 years of age were randomized 2:1 to linezolid or vancomycin. Patients received linezolid 10 mg/kg iv every 8 h with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h or iv vancomycin 10 to 15 mg/kg every 6 to 24 h. Clinical response was evaluated at follow-up. Results from an analysis of patients with HAP or bacteremia are presented. Results. Thirty-nine patients (linezolid, 23; vancomycin, 16) with HAP and 113 patients with bacteremia (linezolid, 81; vancomycin, 32) were included in the intent-to-treat group. Clinical cure rates for clinically evaluable patients with HAP did not differ between treatment groups (linezolid, 90.0% and vancomycin, 100%; P = 0.305). No significant difference was seen in clinical cure rates in the clinically evaluable population between the linezolid and vancomycin groups for patients with catheter-related bacteremia (84.8 and 80.0%, respectively; P = 0.716) or patients with bacteremia of unknown source (79.2 and 69.2%, respectively; P = 0.501). In this subset fewer linezolid-treated patients had drug-related adverse events than did vancomycin-treated patients (19.4%vs. 28.3%; P = 0.230). Similar percentages of patients with laboratory abnormalities, including selected hematologic parameters, were seen in both treatment groups. Conclusions. Intravenous/oral linezolid was well-tolerated and as effective as vancomycin in treating children with resistant Gram-positive HAP or bacteremia.
Efficacy of postoperative epidural analgesia: a meta-analysis.

CONTEXT Whether epidural analgesia is a better method than parenteral opioids for postoperative pain control remains controversial. OBJECTIVE To systematically review the efficacy of postoperative epidural analgesia vs parenteral opioids, the primary alternative technique. DATA SOURCES Studies were identified primarily by searching the National Library of Medicine's PubMed database (1966 to April 25, 2002) and other sources for studies related to postoperative epidural analgesia. STUDY SELECTION Inclusion criteria were a comparison of epidural therapy vs parenteral opioids for postoperative analgesia, measurement of pain using a visual analog scale (VAS) or numeric rating scale, randomization of patients to either therapy, and adult patients (> or =18 years). A total of 1404 abstracts were identified, 100 of which met all inclusion criteria. DATA EXTRACTION Each article was reviewed and data extracted from tables, text, or extrapolated from figures as needed. Weighted mean pain scores, weighted mean differences in pain score, and weighted incidences of complications were determined by using a fixed-effect model. DATA SYNTHESIS Epidural analgesia provided better postoperative analgesia compared with parenteral opioids (mean [SE], 19.40 mm [0.17] vs 29.40 mm [0.20] on the VAS; P<.001). When analyzed by postoperative day, epidural analgesia was better than parenteral opioids on each postoperative day (P<.001 for each day after surgery). For all types of surgery and pain assessments, all forms of epidural analgesia provided significantly better postoperative analgesia compared with parenteral opioid analgesia (P<.001 for all), with the exception of thoracic epidural analgesia vs opioids for rest pain after thoracic surgery (weighted mean difference, 0.6 mm; 95% confidence interval, -0.3 to 1.5 mm; P =.12). The complication rates were lower than expected for nausea or vomiting and pruritus but comparable with existing data for lower extremity motor block. CONCLUSION Epidural analgesia, regardless of analgesic agent, location of catheter placement, and type and time of pain assessment, provided better postoperative analgesia compared with parenteral opioids.
Energy storage to improve reliability of wind integrated systems under frequency security constraint

The integration of wind power into the grid causes numerous stability and reliability issues due to its low inertia and intermittent nature. To ensure system stability, wind power production has to be restricted, which implies that the system cannot absorb the entire output available from wind generation, especially if the output is high. Consequently, the reliability of the integrated system is adversely affected. In order to improve the system reliability, energy storage can be used, which is emerging as a prominent solution for enhancing supply continuity. The complete utilization of an energy storage device can be achieved if it is properly coordinated with wind and conventional generation. This paper proposes a new method to coordinate energy storage with the existing system to improve the system reliability while maintaining the system frequency security. The effectiveness of the model is demonstrated on the IEEE RTS-79 system.
Generation Y and Job Performance: SMEs in Malaysia

The aim of the present study is to examine the impact of personal characteristics namely: physical activity, smoking, drinking, and duration of computer use before taking breaks on performance at work of the “Generation Y” who employed in the Malaysian SMEs. The correlation analyses performed in order to gauge the relationship between individual characteristics and the performance of the 67 respondents who were working at the various SMEs. The key finding indicates that smoking found to have the highest effect. Therefore, this study filled the research gap pertaining to the effective management of manpower in the Malaysian SMEs. Keywords: Individual characteristics; Generation Y; office workers; SMEs; job performance. eISSN 2514-7528 © 2018. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open-access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/jabs.v3i10. 307
Seizure-Induced Changes in Place Cell Physiology: Relationship to Spatial Memory

Status epilepticus (SE) is a frequent neurological emergency associated with a significant risk of morbidity in survivors. Impairment of hippocampal-specific memory is a common and serious deficit occurring in many of the survivors. However, the pathophysiological basis of cognitive deficits after SE is not clear. To directly address the cellular concomitants of spatial memory impairment, we recorded the activity of place cells from CA1 in freely moving rats subjected to SE during early development and compared this activity to that in control rats. Place cells discharge rapidly only when the rat's head is in a cell-specific part of the environment called the “firing field. ” This firing field remains stable over time. Normal place cell function seems to be essential for stable spatial memory for the environment. We, therefore, compared place cell firing patterns with visual-spatial memory in the water maze in SE and control rats. Compared with controls, place cells from the SE rats were less precise and less stable. Concordantly, the water maze performance was also impaired. There was a close relationship between precision and stability of place cells and water maze performance. In contrast, a single, acute, chemically induced seizure produced cessation of place cell activity and spatial memory impairment in water maze performance that reversed within 24 hr. These results strongly bolster the idea that there is a relationship between abnormal place cells and spatial memory. Our findings also suggest that the defects in place cell and spatial memory after SE and acute chemically induced seizures result from different processes.
Effect of cross-level interaction between individual and neighborhood socioeconomic status on adult mortality rates.

OBJECTIVE We examined whether the influence of neighborhood-level socioeconomic status (SES) on mortality differed by individual-level SES. METHODS We used a population-based, mortality follow-up study of 4476 women and 3721 men, who were predominately non-HIspanic White and aged 25-74 years at baseline, from 82 neighborhoods in 4 California cities. Participants were surveyed between 1979 and 1990, and were followed until December 31, 2002 (1148 deaths; mean follow-up time 17.4 years). Neighborhood SES was defined by 5 census variables and was divided into 3 levels. Individual SES was defined by a composite of educational level and household income and was divided into tertiles. RESULTS Death rates among women of low SES were highest in high-SES neighborhoods (1907/100000 person-years), lower in moderate-SES neighborhoods (1323), and lowest in low-SES neighborhoods (1128). Similar to women, rates among men of low SES were 1928, 1646, and 1590 in high-, moderate-, and low-SES neighborhoods, respectively. Differences were not explained by individual-level baseline risk factors. CONCLUSION The disparities in mortality by neighborhood of residence among women and men of low SES demonstrate that they do not benefit from the higher quality of resources and knowledge generally associated with neighborhoods that have higher SES.
Fault tolerant Active Neutral Point Clamped inverter: Short-circuit and open-circuit failures

This paper investigates the fault-tolerant capacity of a modified three-level Active Neutral Point Clamped (ANPC) inverter when its switches are submitted to open and short-circuit failures. The main change consists on adding a thyristor in parallel with each inverter switch. This improves the behavior of the converter when a switch fails. Fault detection and identification methods are presented together with configured schemes for ten types of failures. Simulation and experimental results validate the theoretical studies.