Miracle-dz/UniFAR-FTUs huggingface dataset:
The natural history of early versus late disability accumulation in primary progressive MS

Background Primary progressive multiple sclerosis (PPMS) is the least common MS disease course and carries the worst prognosis. In relapsing–remitting multiple sclerosis (RRMS) disability accumulation occurs in two distinct phases, but it is unclear whether this is also true for PPMS. Here we investigate factors associated with early and late disability accumulation in PPMS. Methods We used Kaplan–Meier survival analyses and Cox regression to investigate the influence of sex, age at disease onset and onset symptoms on time to, and age at, Expanded Disability Status Scale (EDSS) 4 and 6, as well as the time from EDSS 4 to 6 in patients with PPMS. Results We identified 500 patients with PPMS. The analyses on time to EDSS 4 included 358 patients, and those on time to EDSS 6 included 392 patients. The median times to EDSS 4 and EDSS 6 were 5 and 9 years. The analyses on age at EDSS 4 included 360 patients, and those on age at EDSS 6 included 402 patients. The median ages at EDSS 4 and EDSS 6 were 51 and 55 years. Older age at onset and bilateral motor onset symptoms were independently associated with a shorter time to both EDSS 4 and EDSS 6. Sex and other onset symptoms were not associated with time to, or age at, landmark disability. Only age at onset was significantly associated with the time from EDSS 4 to EDSS 6. Conclusions Age at disease onset is the most important predictor of disability accumulation in PPMS. Bilateral motor onset symptoms were associated with quicker disease progression. In contrast to RRMS, we found no evidence for distinct phases of disability accumulation in PPMS. Disability accumulation in PPMS appears to be affected by the same factors throughout its course.
Seroprevalence and risk factors of Hepatitis C Virus in patients and blood donors in Kano, Nigeria

Hepatitis C virus (HCV) is a major cause of chronic liver disease resulting in cirrhosis and hepatocarcinoma. It is believed to be widespread in Africa but its epidemiology is incomplete and is yet to be determined in many areas of the sub-saharan Africa including Nigeria. Using third generation enzyme immuno-assay (EIA-3) and recombinant immunoblot assay (RIBA) technique as confirmatory test, we examined the prevalence of HCV antibodies in 226 blood donors and 226 patients attending Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria and evaluated the risk factors of HCV transmission in this environment. HCV antibodies were detected in 0.4% and 2.2% blood donors and patients respectively. The overall HCV seroprevalence was 1.3%. There was increased infection acquisition with increasing age; one (16.7%) HCV infection occurred in 25-34 years age group and 5 or 83.3% in subjects > 45 years in age which was significant (P Key words: Hepatitis C virus, seroprevalence, patients, blood donors, risk factors.
Type I diabetes mellitus decreases in vivo macrophage-to-feces reverse cholesterol transport despite increased biliary sterol secretion in mice

Type I diabetes mellitus (T1DM) increases atherosclerotic cardiovascular disease; however, the underlying pathophysiology is still incompletely understood. We investigated whether experimental T1DM impacts HDL-mediated reverse cholesterol transport (RCT). C57BL/6J mice with alloxan-induced T1DM had higher plasma cholesterol levels (P < 0.05), particularly within HDL, and increased hepatic cholesterol content (P < 0.001). T1DM resulted in increased bile flow (2.1-fold; P < 0.05) and biliary secretion of bile acids (BA, 10.5-fold; P < 0.001), phospholipids (4.5-fold; P < 0.001), and cholesterol (5.5-fold; P < 0.05). Hepatic cholesterol synthesis was unaltered, whereas BA synthesis was increased in T1DM (P < 0.001). Mass fecal BA output was significantly higher in T1DM mice (1.5-fold; P < 0.05), fecal neutral sterol excretion did not change due to increased intestinal cholesterol absorption (2.1-fold; P < 0.05). Overall in vivo macrophage-to-feces RCT, using [3H]cholesterol-loaded primary mouse macrophage foam cells, was 20% lower in T1DM (P < 0.05), mainly due to reduced tracer excretion within BA (P < 0.05). In vitro experiments revealed unchanged cholesterol efflux toward T1DM HDL, whereas scavenger receptor class BI-mediated selective uptake from T1DM HDL was lower in vitro and in vivo (HDL kinetic experiments) (P < 0.05), conceivably due to increased glycation of HDL-associated proteins (+65%, P < 0.01). In summary, despite higher mass biliary sterol secretion T1DM impairs macrophage-to-feces RCT, mainly by decreasing hepatic selective uptake, a mechanism conceivably contributing to increased cardiovascular disease in T1DM.
C323 of SR-BI is required for SR-BI-mediated HDL binding and cholesteryl ester uptake[S]

Scavenger receptor BI (SR-BI) is an HDL receptor. It binds HDL and mediates the uptake of cholesteryl ester from HDL. Early studies have pointed out that the extracellular domain of SR-BI is critical for SR-BI-mediated cholesteryl ester uptake. However, the extracellular loop of SR-BI is large: it contains 403 amino acids. The HDL binding site and the modulation of SR-BI-mediated cholesteryl ester uptake remain to be identified. In this study, using C323G mutant SR-BI, we showed that C323G mutant SR-BI lost its HDL binding and cholesteryl ester uptake activity, indicating that the highly conserved C323 is required for SR-BI-mediated HDL binding and cholesteryl ester uptake. Using a blocking antibody against C323 region, we demonstrated that C323 is directly involved in HDL binding and likely an HDL binding site. Using C323G mutant transgenic mouse model, we further demonstrated that C323 of SR-BI is required for regulating plasma cholesterol levels in vivo. Using redox reagents, we showed that physiological relevant levels of H2O2 upregulated the SR-BI-mediated cholesteryl ester uptake activity by 65%, whereas GSH or DTT significantly downregulated SR-BI-mediated cholesteryl ester uptake activity by 45%. C323 of SR-BI is critical for SR-BI-mediated HDL binding and cholesteryl ester uptake, and changes in redox status may be a regulatory factor modulating SR-BI-mediated cholesterol transport.
Coding k-ary trees for efficient loopless generation in lexicographic order

In this paper, e-words are used for coding k-ary trees with n internal nodes. The properties of e-words are discussed in depth, such as the necessary and sufficient condition of e-words, and based on the properties, a loopless algorithm is obtained to generate e-words for k-ary trees in lexicographic order, which is more efficient in both space and time than the previous algorithm. In addition, e-words can also be easily generated in lexicographic order by a recursive algorithm, and in the order with the Strong Minimal Change Property (SMCP) by a loopless algorithm.
Overlapping CNS inflammatory diseases: differentiating features of NMO and MS

Neuromyelitis optica (NMO) has long been considered as a variant of multiple sclerosis (MS) rather than a distinct disease. This concept changed with the discovery of serum antibodies (Ab) against aquaporin-4 (AQP4), which unequivocally differentiate NMO from MS. Patients who test positive for AQP4-Abs and present with optic neuritis (ON) and transverse myelitis (TM) are diagnosed with NMO and those who show an incomplete phenotype with isolated ON or longitudinally extensive TM (LETM) or less commonly brain/brainstem disease are referred to as NMO spectrum disorders (NMOSD). However, many patients, who have overlapping features of both NMO and MS, test negative for AQP4-Abs and may be difficult to definitively diagnose. This raises important practical issues, since NMO and MS respond differently to immunomodulatory treatment and have different prognoses. Here we review distinct features of AQP4-positive NMO and MS, which might then be useful in the diagnosis of antibody-negative overlap syndromes. We identify discriminators, which are related to demographic data (non-white origin, very late onset), clinical features (limited recovery from ON, bilateral ON, intractable nausea, progressive course of disability), laboratory results (cerebrospinal fluid (CSF) pleocytosis with eosinophils and/or neutrophils, oligoclonal bands, glial fibrillary acidic protein in the CSF) and imaging (LETM, LETM with T1 hypointensity, periependymal brainstem lesions, perivenous white matter lesions, Dawson's fingers, curved or S-shaped U-fibre juxtacortical lesions). We review the value of these discriminators and discuss the compelling need for new diagnostic markers in these two autoimmune demyelinating diseases of the central nervous system.
Molecular simulation of rapid translocation of cholesterol, diacylglycerol, and ceramide in model raft and nonraft membranes[S]

The translocation of lipids across membranes (flip-flop) is an important biological process. Slow exchange on a physiological timescale allows the creation of asymmetric distributions of lipids across cellular membranes. The location of lipids and their rate of exchange have important biological consequences, especially for lipids involved in cellular signaling. We investigated the translocation of cholesterol, ceramide, and diacylglycerol in two model bilayers using molecular dynamics simulations. We estimate half times for flip-flop for cholesterol, diacylglycerol, and ceramide of 20 μs, 30 μs, and 10 ms in a POPC bilayer, compared with approximately 30 min, 30 ms, and 30 s in a model raft bilayer (1:1:1 PSM, POPC, and cholesterol). Cholesterol has a large (54 kJ/mol) free energy of exchange between the POPC and raft bilayer, and therefore, it strongly prefers the more ordered and rigid raft bilayer over the more liquid POPC bilayer. Ceramide and diacylglycerol have relatively small free energies of exchange, suggesting nearly equal preference for both bilayers. This unexpected result may have implications for ceramide and diacylglycerol signaling and membrane localization.
Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient to prevent diet-induced cholesterol accumulation in the liver and blood[S]

Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) generates cholesterol esters (CE) for packaging into newly synthesized lipoproteins and thus is a major determinant of blood cholesterol levels. ACAT2 is expressed exclusively in the small intestine and liver, but the relative contributions of ACAT2 expression in these tissues to systemic cholesterol metabolism is unknown. We investigated whether CE derived from the intestine or liver would differentially affect hepatic and plasma cholesterol homeostasis. We generated liver-specific (ACAT2L−/L−) and intestine-specific (ACAT2SI−/SI−) ACAT2 knockout mice and studied dietary cholesterol-induced hepatic lipid accumulation and hypercholesterolemia. ACAT2SI−/SI− mice, in contrast to ACAT2L−/L− mice, had blunted cholesterol absorption. However, specific deletion of ACAT2 in the intestine generated essentially a phenocopy of the conditional knockout of ACAT2 in the liver, with reduced levels of plasma very low-density lipoprotein and hepatic CE, yet hepatic-free cholesterol does not build up after high cholesterol intake. ACAT2L−/L− and ACAT2SI−/SI− mice were equally protected from diet-induced hepatic CE accumulation and hypercholesterolemia. These results suggest that inhibition of intestinal or hepatic ACAT2 improves atherogenic hyperlipidemia and limits hepatic CE accumulation in mice and that depletion of intestinal ACAT2 is sufficient for most of the beneficial effects on cholesterol metabolism. Inhibitors of ACAT2 targeting either tissue likely would be beneficial for atheroprotection.
Progression of cognitive impairments in idiopathic REM sleep behaviour disorder

Background Idiopathic REM (rapid eye movement) sleep behaviour disorder (iRBD) has been implicated in cognitive impairments, but there is little evidence about progression of cognitive dysfunction in iRBD. Methods A retrospective follow-up study with patients with iRBD was performed. Conversion to neurodegenerative disorders was analysed by Kaplan-Meier survival analysis. Neuropsychological test results at baseline were compared between patients with iRBD and healthy controls. 57 patients with iRBD were successfully followed up for changes of cognitive performance over time (follow-up duration 50.84±25.38 months; range 12–108 months). Factors affecting cognitive decline were evaluated with multiple regression analysis and the subgroup analysis for groups with and without conversion was carried out. Results Among 84 patients with iRBD, conversion occurred in 18 patients and conversion rates were estimated to be 9%, 18% and 35% at 3, 5 and 6 years from diagnosis of iRBD. Individuals with iRBD showed lower z-scores at baseline than controls in Mini-Mental Status Examination, Trail Making Test A, constructional praxis and Executive Clock Drawing Task (CLOX2). Patients with non-converting iRBD showed significant performance decline in memory (p=0.003, Digit span forward) and a worsening tendency of executive functions (p=0.007, frontal assessment battery; p=0.012, Stroop test) at follow-up tests. Cognitive decline was associated with disease duration or follow-up duration, and lower executive function at baseline increased conversion risk (p=0.031). Conclusions Patients with iRBD have cognitive impairments at baseline and progressive cognitive decline over time. Even in idiopathic cases without development of any neurodegenerative disease, degenerative changes in cognition seem to be under way.
Habitual patterns of physical activity during pregnancy and postnatally

Few British studies appear to follow expectant mothers through the gestative period and study patterns of activity during all three trimesters of pregnancy and after birth. This study set out to investigate patterns of physical activity throughout pregnancy and after birth in women living in London. Using the International Physical Activity Questionnaire, physical activity levels were assessed at weeks 13, 25, 35 of pregnancy and 6 weeks postpartum. Ninety-four primiparous pregnant women were recruited at the study start and 70, 58, 59 and 54 completed the first, second, third trimester and postpartum study stages respectively. Women undertook most vigorous activity in the first trimester of pregnancy (29.8mins per day). Up to 5 kcal per kg per day of energy was expended through participation in home activities after birth. This study demonstrates that domains of activity change as pregnancy progresses and that household activity plays a key role in contributing to energy expenditure, particularly after b.
GPSF: General-Purpose Scheduling Framework for Container Based on Cloud Environment

Currently, container technology has increasingly grown up in cloud environment. However, the research related with resource management for container has not been considered actively. To manage resources on cloud with container efficiently, we present the GPSF, General-Purpose Scheduling Framework. This framework provides useful resource management functions, and more importantly it is possible to apply customized scheduling in local environment. By using the framework, cloud providers or researchers can optimize resources for their purpose. We implement a prototype of the GPSF and evaluate it by applying customized scheduling. Our results show that it works correctly and it is easy to use enough. So we believe that it has a great potential as optimizing resources for container technology.
Evaluation of renal biopsies in cats and dogs — histopathology in comparison with clinical data

Histopathological findings of renal biopsies in cats and dogs with diffuse nephropathies generally lead to an exact diagnosis and facilitate prognostic judgements. Complications following renal biopsy are usually slight, provided the biopsy is performed properly. Routine renal laboratory data have been compared with histopathological findings. High urine protein values are often the result of glomerular lesions, whereas high creatinine values are frequently related to tubulointerstitial lesions. In general, there is no relationship between different types of nephropathy and age; nevertheless animals with chronic tubulointerstitial nephritis were, on average, older than animals with glomerulopathies.
Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases

Background Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. Methods Summary statistics were obtained from the International FTD Genomics Consortium, International PD Genetics Consortium and International Genomics of AD Project (n>75 000 cases and controls). We used conjunction false discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-associated SNPs. Relevant variants were further evaluated for expression quantitative loci. Results We observed SNPs within the HLA, MAPT and APOE regions jointly contributing to increased risk for FTD and AD or PD. By conditioning on polymorphisms associated with PD and AD, we found 11 loci associated with increased risk for FTD. Meta-analysis across two independent FTD cohorts revealed a genome-wide signal within the APOE region (rs6857, 3′-UTR=PVRL2, p=2.21×10–12), and a suggestive signal for rs1358071 within the MAPT region (intronic=CRHR1, p=4.91×10−7) with the effect allele tagging the H1 haplotype. Pleiotropic SNPs at the HLA and MAPT loci associated with expression changes in cis-genes supporting involvement of intracellular vesicular trafficking, immune response and endo/lysosomal processes. Conclusions Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk.
Record Setting Software Implementation of DES Using CUDA

The increase in computational power of off-the-shelf hardware offers more and more advantageous tradeoffs among efficiency, cost and availability, thus enhancing the feasibility of of cryptanalytic attacks aiming to lower the security of widely used cryptosystems. In this paper we illustrate an GPU-based software implementation of the most efficent variant of Data Encryption Standard (DES), showing the performance of a software breaker which effectively exploits the multi-core Nvidia GT200 graphic architecture. The key point is to assess how well the structure of a symmetric key cipher can fit the GPU programming model and the single instruction multiple data architectural parallelism. The proposed breaker outperforms the fastest general purpose CPU-based implementations by an order of magnitude, and, due to the vast availability of GPUs on the market, the speedup translates into a sound improvement in the cost efficiency of the attack. As opposed to solutions based either on application specific or reconfigurable hardware, the proposed implementation does not require any specific technical knowledge from the attacker in order to be successfully built, once our implementation is available. This turns out in a better cost-availability tradeoff and minimizes the required setup time for such an attack to be mounted.
'Do I really have to eat that?': A qualitative study of schoolchildren's food choices and preferences

This study, conducted in 1994, set out to explore food preferences, eating behaviour and food choice with Primary 7 children (mean age 11 years) in a small primary school in Edinburgh. A qualitative methodological approach was adopted, utilising focus groups and observational techniques. Analysis of the data indicated food choice was not determined by the health attributes of food but rather that values of preference, play, socialisation and convenience were given a higher priority than health by the children when making food choices. 'Healthy' foods were found to be associated with the concept of a proper meal and homemade foods. A different classification of foods based on like and dislike was proposed to explain children's food choice.
Nodes, paranodes and neuropathies

This review summarises recent evidence supporting the involvement of the specialised nodal and perinodal domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammatory, peripheral neuropathies. The identification of new target antigens in the inflammatory neuropathies heralds a revolution in diagnosis, and has already begun to inform increasingly targeted and individualised therapies. Rapid progress in our basic understanding of the highly specialised nodal regions of peripheral nerves serves to strengthen the links between their unique microstructural identities, functions and pathologies. In this context, the detection of autoantibodies directed against nodal and perinodal targets is likely to be of increasing clinical importance. Antiganglioside antibodies have long been used in clinical practice as diagnostic serum biomarkers, and associate with specific clinical variants but not to the common forms of either acute or chronic demyelinating autoimmune neuropathy. It is now apparent that antibodies directed against several region-specific cell adhesion molecules, including neurofascin, contactin and contactin-associated protein, can be linked to phenotypically distinct peripheral neuropathies. Importantly, the immunological characteristics of these antibodies facilitate the prediction of treatment responsiveness.
Relative roles of ABCG5/ABCG8 in liver and intestine

ABCG5 (G5) and ABCG8 (G8) form a sterol transporter that acts in liver and intestine to prevent accumulation of dietary sterols. Mutations in either G5 or G8 cause sitosterolemia, a recessive disorder characterized by sterol accumulation and premature coronary atherosclerosis. Hepatic G5G8 mediates cholesterol excretion into bile, but the function and relative importance of intestinal G5G8 has not been defined. To determine the role of intestinal G5G8, we developed liver-specific (L-G5G8−/−), intestine-specific (I-G5G8−/−), and total (G5G8−/−) KO mice. Tissue levels of sitosterol, the most abundant plant sterol, were >90-fold higher in G5G8−/− mice than in WT animals. Expression of G5G8 only in intestine or only in liver decreased tissue sterol levels by 90% when compared with G5G8−/− animals. Biliary sterol secretion was reduced in L-G5G8−/− and G5G8−/− mice, but not in I-G5G8−/− mice. Conversely, absorption of plant sterols was increased in I-G5G8−/− and G5G8−/− mice, but not in L-G5G8−/− mice. Reverse cholesterol transport, as assessed from the fraction of intravenously administered 3H-cholesterol that appeared in feces, was reduced in G5G8−/−, I-G5G8−/−, and L-G5G8−/− mice. Thus, G5G8 expression in both the liver and intestine protects animals from sterol accumulation, and intestinal G5G8 contributes to extrahepatic cholesterol efflux in mice.