Miracle-dz/UniFAR-FTUs huggingface dataset:
Seizure recurrence after antiepileptic drug withdrawal and the implications for driving: further results from the MRC Antiepileptic Drug Withdrawal Study and a systematic review

Background In the UK, patients with epilepsy in remission, who withdraw antiepileptic drug (AED) treatment, are advised not to drive during withdrawal and for 6 months thereafter, assuming the risk of recurrence in the next 12 months is below 20%. Those with a seizure recurrence currently have to be seizure-free for 12 months before returning to drive, whether treatment is restarted or not. New EU regulations recommend returning to driving 3 months after restarting treatment. Methods Regression modelling of data from the Medical Research Council AED withdrawal study was undertaken to estimate the risk of seizure recurrence in the next 12 months at various time points following: completion of drug withdrawal; AED reinstatement for those with a recurrence. A systematic review of prospective studies was also undertaken. Results Immediately following treatment withdrawal, the recurrence risk in the next 12 months was 30% (95% CI 25% to 35%) and at 3 months after withdrawal was 15% (95% CI 10% to 19%). At 3 months following the recommencement of treatment following a seizure recurrence, the risk of a seizure in the next 12 months was 26% (95% CI 17% to 35%), at 6 months 18% (95% CI 10% to 27%) and at 12 months 17% (95% CI 3% to 27%). Systematic review results were similar. Conclusion Current UK legislation concerning time off driving after withdrawing AED treatment may be too conservative. For those restarting treatment after a recurrence, current UK guidance may be too conservative but the new EU guidance too liberal.
The host microRNA miR-301a blocks the IRF1-mediated neuronal innate immune response to Japanese encephalitis virus infection

Targeting a microRNA that inhibits type I interferon production may be a strategy to treat Japanese encephalitis virus infection. Fighting flavivirus infection Japanese encephalitis virus (JEV), which is related to the Zika, West Nile, and dengue viruses, targets the central nervous system, causing viral encephalitis. Because of the high mortality rate in JEV-infected individuals and the neurological damage that afflicts survivors, effective antiviral therapies are urgently needed. Hazra et al. found that JEV infection of mouse and human neuronal cells increased the abundance of the microRNA miR-301a, which inhibited the cells from producing type I interferons (IFNs), cytokines that are critical to the antiviral immune response. One of the targets of miR-301a is the transcription factor IRF1, which is required for the expression of genes encoding type I IFNs. Treating JEV-infected mice with an inhibitor of miR-301a restored IRF1 abundance and function and led to increased type I IFN production, decreased viral replication, and increased survival. Together, these data suggest that targeting miR-301a may be an effective therapy against JEV infection. Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of the Flaviviridae family that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes. We showed that the JEV-induced expression of miR-301a led to inhibition of the production of type I IFN by reducing the abundances of the transcription factor IFN regulatory factor 1 (IRF1) and the signaling protein suppressor of cytokine signaling 5 (SOCS5). Mechanistically, induction of miR-301a expression during JEV infection required the transcription factor nuclear factor κB. In mouse neurons, neutralization of miR-301a restored the host innate immune response by enabling IFN-β production, thereby restricting viral propagation. Inhibition of miR-301a in mouse brain rescued the production of IRF1 and SOCS5, increased the generation of IFN-β, and reduced the extent of JEV replication, thus improving mouse survival. Thus, our study suggests that the JEV-induced expression of miR-301a assists viral pathogenesis by suppressing IFN production, which might be targeted by antiviral therapies.
Two-Stage Pretreatment to Improve Saccharification of Oat Straw and Jerusalem Artichoke Biomass

Pretreatment is a necessary step when lignocellulosic biomass is to be converted to simple sugars; however single-stage pretreatment is often insufficient to guarantee full availability of polymeric sugars from raw material to hydrolyzing enzymes. In this work, the two-stage pretreatment with use of acid (H2SO4, HNO3) and alkali (NaOH) was applied in order to increase the susceptibility of Jerusalem artichoke stalks (JAS) and oat straw (OS) biomass on the enzymatic attack. The effect of the concentration of reagents (2% and 5% w/v) and the order of acid and alkali sequence on the composition of remaining solids and the efficiency of enzymatic hydrolysis was evaluated. It was found that after combined pretreatment process, due to the removal of hemicellulose and lignin, the content of cellulose in pretreated biomass increased to a large extent, reaching almost 90% d.m. and 95% d.m. , in the case of JAS and OS, respectively. The enzymatic hydrolysis of solids remaining after pretreatment resulted in the formation of up to 45 g/L of glucose, for both JAS and OS. The highest glucose yield was achieved after pretreatment with 5% nitric acid followed by NaOH, and 90.6% and 97.6% of efficiency were obtained, respectively for JAS and OS.
Prenatal Diagnosis of Parvovirus B19-Induced Hydrops Fetalis by Chemiluminescence In Situ Hybridization

ABSTRACT Parvovirus B19 can be transmitted transplacentally from the infected mother to the fetus during pregnancy, and hydrops fetalis, abortion, or stillbirth can result. In our study we explored the use of chemiluminescence in situ hybridization to detect B19 DNA on cord blood cells, amniotic fluid cells, and pleuric fluid cells from several cases of hydrops fetalis. B19 DNA was detected by using digoxigenin-labeled probes immunoenzymatically visualized with the chemiluminescent adamantil-1,2-dioxetane phenyl phosphate substrate for alkaline phosphatase. The luminescent signal emitted from the hybridized probes was detected, analyzed, and measured with a high-performance, low-light-level imaging luminograph connected to an optical microscope and to a personal computer for the quantification and localization of the chemiluminescent emission inside individual cells.
Crystal structure of (2S/2R,3S/3R)-3-hydroxy-2-phenylchroman-4-one

In the title molecule, C15H12O3, the C atoms bearing the hydroxy group and the phenyl ring are disordered over two sets of sites with refined occupancies of 0.573 (7) and 0.427 (7). There is also disorder of the phenyl ring but the hydroxy group was refined as ordered. The dihedral angles between the benzene ring of the chromane ring system and the phenyl ring are 89.7 (2)° for the major component of disorder and 72.1 (3)° for the minor component. Both disorder components of the the dihydropyran ring are in a half-chair conformation. In the crystal, molecules are linked by pairs of O—H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(10) graph-set motif. Weak C—H⋯π interactions link these dimers into ladders along [001].
Glycosylphosphatidylinositol (GPI) anchor is required in Aspergillus fumigatus for morphogenesis and virulence

In yeast, glycosylphosphatidylinositol (GPI) is essential for viability and plays an important role in biosynthesis and organization of cell wall. Initiation of the GPI anchor biosynthesis is catalysed by the GPI–N‐acetylglucosaminyltransferase complex (GPI–GnT). The GPI3 (SPT14) gene is thought to encode the catalytic subunit of GPI–GnT complex. In contrast to Saccharomyces cerevisiae, little is known about the GPI biosynthesis in filamentous fungi. In this study, the afpig‐a gene was identified as the homologue of the GPI3/pig‐A gene in Aspergillus fumigatus, an opportunistic fungal pathogen. By replacement of the afpig‐a gene with a pyrG gene, we obtained the null mutants. Although the Δafpig‐a mutant exhibited a significant increased cell lysis instead of temperature‐sensitive or conditional lethal phenotype associated to the GPI3 mutant of yeast, they could survive at temperatures from 30°C to 50°C. The analysis of the mutants showed that a completely blocking of the GPI anchor synthesis in A. fumigatus led to cell wall defect, abnormal hyphal growth, rapid conidial germination and aberrant conidiation. In vivo assays revealed that the mutant exhibited a reduced virulence in immunocompromised mice. The GPI anchor was not essential for viability, but required for the cell wall integrity, morphogenesis and virulence in A. fumigatus.
Total energy expenditure is comparable between patients with and without diabetes mellitus: Clinical Evaluation of Energy Requirements in Patients with Diabetes Mellitus (CLEVER-DM) Study

Objective Assessment of total energy expenditure (TEE) is essential for appropriate recommendations regarding dietary intake and physical activity in patients with and without diabetes mellitus (DM). However, few reports have focused on TEE in patients with DM, particularly in Asian countries. Therefore, we evaluated TEE in Japanese patients with DM using the doubly labeled water (DLW) method and physical activity level (PAL). Research design and methods In this cross-sectional observational study, we evaluated 52 patients with type 2 DM and 15 patients without DM. Free-living TEE was measured over 12–16 days by the DLW method, and PAL was calculated as TEE divided by the basal metabolic rate (BMR) as assessed by indirect calorimetry. The equivalence margin was defined as 5 kcal/kg/day. Results The numbers of patients with DM treated with insulin, oral antidiabetic drugs, and diet were 18 (34.6%), 20 (38.5%), and 14 (26.9%), respectively. The mean±SD level of glycated hemoglobin was 6.9%±0.8% and 5.5%±0.3% in the DM and non-DM group, respectively (p<0.001). The mean body mass index was 23.3±3.0 and 22.7±2.1 kg/m2 in the DM and non-DM group, respectively. The mean TEE per kilogram body weight adjusted for sex and age was 36.5 kcal/kg/day and 37.5 kcal/kg/day in the DM and non-DM group, respectively, with no significant difference (mean difference, −1.0 kcal/kg/day; 95% CI -4.2 to 2.3 kcal/kg/day). The BMR tended to be higher in the DM than in the non-DM group (mean difference, 33 kcal/day; 95% CI, −15 to 80 kcal/day). The mean PAL adjusted for sex and age was 1.71 and 1.81 in the DM and non-DM group, respectively, without a significant difference (mean difference, −0.10; 95% CI −0.21 to 0.01). Conclusion TEE was comparable between Japanese patients with and without DM. Trial registration number UMIN000023051.
Similar Ultrastructural Breakdown of Cerebrocortical Capillaries in Alzheimer's Disease, Parkinson's Disease, and Experimental Hypertension: What is the Functional Link?

Abstract: The brain, as an intensely active organ, is highly dependent on a sufficient nutrient and oxygen availability in order to reach its optimal working capacity. It is well known that the vital supply of energy substrates is provided by the circulatory system, which splits up into a fine, terminal capillary network in target tissues. These capillaries are considered as important sites, since the actual nutrient trafficking takes place through their walls. That is why an intact, preserved structure of the microvessels is crucial to fulfill their function. Since the brain is known to be particularly vulnerable to suboptimal oxygen and glucose delivery, the intact morphology of capillaries is of paramount importance.
Learning Depth from Monocular Videos Using Direct Methods

The ability to predict depth from a single image - using recent advances in CNNs - is of increasing interest to the vision community. Unsupervised strategies to learning are particularly appealing as they can utilize much larger and varied monocular video datasets during learning without the need for ground truth depth or stereo. In previous works, separate pose and depth CNN predictors had to be determined such that their joint outputs minimized the photometric error. Inspired by recent advances in direct visual odometry (DVO), we argue that the depth CNN predictor can be learned without a pose CNN predictor. Further, we demonstrate empirically that incorporation of a differentiable implementation of DVO, along with a novel depth normalization strategy - substantially improves performance over state of the art that use monocular videos for training.
Behavior of solid carbon sources for biological denitrification in groundwater remediation.

The present study was conducted to compare the behavior of wheat straw, sawdust and biodegradable plastic (BP) as potential carbon sources for denitrification in groundwater remediation. The results showed that a greater amount of nitrogen compounds were released from wheat straw and sawdust than from BP in leaching experiments. In batch experiments, BP showed higher nitrate removal efficiency and longer service life than wheat straw and sawdust, which illustrated that BP is the most appropriate carbon source for stimulation of denitrification activity. In column experiments, BP was able to support complete denitrification at influent nitrate concentrations of 50, 60, 70, 80, and 90 mg NO(3)(-)-N/L, showing corresponding denitrification rates of 0.12, 0.14, 0.17, 0.19, and 0.22 mg NO(3)(-)-N.L(-1). d(-1). g(-1), respectively. These findings indicate that BP is applicable for use as a carbon source for nitrate-polluted groundwater remediation.
Risk assessment in professional football: an examination of accidents and incidents in the 1994 World Cup finals.

OBJECTIVE: To assess the risks to footballers' health and safety during competitive international matches, with identification of the most common causes of injury. METHODS: Videos of 44 of the 52 matches played during the 1994 World Cup finals staged in the USA were analysed. During each match, several relevant variables were recorded, including the number of fouls, injuries, treatments, times of incidents, identity of players treated or injured, and the injury mechanism. Additional information on players' injuries was obtained from the extensive media coverage of the event. RESULTS: Only 29% of injuries resulted from foul play, whereas 71% of injuries to players occurred where no foul play was adjudged by the referee to have taken place (P < 0.01). Defenders were found to be proportionately subjected to a greater risk of injury than other players (P < 0.05). Fifteen per cent of all injuries were judged to be at least moderate, resulting in the player missing at least one match. Frequency of moderate injury was 1026 injuries per 100,000 hours played. CONCLUSIONS: The major causes of injuries during international football matches were not found to be associated with foul play, as judged by the referees. However, in those cases where injuries occurred without a foul being committed, almost 50% involved player to player contact. This gives some cause for concern and is worth further investigation.
Relation of oxidative stress, zinc and alkaline phosphatase in protein energy malnutrition

Objective: To determine serum zinc (Zn), total anti-oxidant capacity (TAC), malondialdehyde (MDA), alkaline phosphatase (ALP) and albumin in protein energy malnutrition (PEM) and to analyse the appropriateness of using low weight-for-age for detecting childhood under-nutrition. Methods: This study comprised 455 children (355 malnourished and 100 normal). They were classified according to the Nutrition Subcommittee of Indian Academy of Pediatrics, Z-Score Classification and Composite Index of Anthropometric Failure. Serum Zn, TAC, MDA, ALP and albumin levels were determined. Results: The serum Zn, TAC, ALP and albumin levels were found to be significantly decreased and MDA levels were significantly increased in malnourished children as compared with control (P < 0.001). Conclusion: The significant increase in serum MDA concentration associated with the decrease in serum TAC, Zn and ALP in malnourished children suggest that these children were potentially susceptible to high oxidative stress. Current study also suggest that conventional measures of detecting under-nutrition (low weight-for-age) may be missing out a considerable proportion of undernourished children present in the population.
A test for stability of linear differential delay equations

The changes in the stability of a system of linear differential delay equations resulting from the delay are studied by analyzing the associated eigenvalues of the characteristic equation. A specific contour is mapped by the characteristic equation into the complex plane to give an easy test for stability from an application of the argument principle. When the real part of an eigenvalue is positive, the contour gives bounds on the imaginary part which are important in certain applications to nonlinear problems.
Treatment of retinal vasculitis in Behçet's disease with rituximab

Behçet's disease (BD) is more common in eastern than western countries. Physicians have frequently encountered problems in its treatment, especially eye involvement. Recurrent oral and genital aphthous ulcerations are the hallmarks of Behçet’s disease but other organs can be involved and ocular disease is one of the most disabling manifestations. Up to now, there are some problems in treatment of the retinal vasculitis due to Behçet’s disease. We reported one patient, with visual loss due to retinal vasculitis that was resistant to prednisolone and azathioprine. Our patient was treated successfully with rituximab and his remission was sustained for 24 months of follow-up. Rituximab is a chimeric monoclonal antibody that acts against the specific B cell antigen, CD20. The recent success of rituximab in autoimmune diseases, which is considered to be T cell-mediated, indicates that B cells must have a much broader role in the pathogenesis of autoimmune diseases than generally appreciated.
Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3.

BACKGROUND Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin. METHODS We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (<50 IU per milliliter) 24 weeks after the end of treatment. RESULTS The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P<0.001). In addition, the rate of relapse (a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment) was significantly greater in the 16-week group (31%, vs. 18% in the 24-week group; P<0.001). The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82% with the 16-week regimen and 81% with the 24-week regimen. Among patients with a rapid virologic response (an undetectable HCV RNA level by week 4), sustained virologic response rates were 79% in the 16-week group and 85% in the 24-week group (P=0.02). CONCLUSIONS Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636 [ClinicalTrials.gov].).
Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern

Activating mutations of the p110 α subunit of PI3K (PIK3CA) oncogene have been identified in a broad spectrum of malignant tumors. However, their role in benign or preneoplastic conditions is unknown. Activating FGF receptor 3 (FGFR3) mutations are common in benign skin lesions, either as embryonic mutations in epidermal nevi (EN) or as somatic mutations in seborrheic keratoses (SK). FGFR3 mutations are also common in low-grade malignant bladder tumors, where they often occur in association with PIK3CA mutations. Therefore, we examined exons 9 and 20 of PIK3CA and FGFR3 hotspot mutations in EN (n = 33) and SK (n = 62), two proliferative skin lesions lacking malignant potential. Nine of 33 (27%) EN harbored PIK3CA mutations; all cases showed the E545G substitution, which is uncommon in cancers. In EN, R248C was the only FGFR3 mutation identified. By contrast, 10 of 62 (16%) SK revealed the typical cancer-associated PIK3CA mutations E542K, E545K, and H1047R. The same lesions displayed a wide range of FGFR3 mutations. Corresponding unaffected tissue was available for four EN and two mutant SK: all control samples displayed a WT sequence, confirming the somatic nature of the mutations found in lesional tissue. Forty of 95 (42%) lesions showed at least one mutation in either gene. PIK3CA and FGFR3 mutations displayed an independent distribution; 5/95 lesions harbored mutations in both genes. Our findings suggest that, in addition to their role in cancer, oncogenic PIK3CA mutations contribute to the pathogenesis of skin tumors lacking malignant potential. The remarkable genotype–phenotype correlation as observed in this study points to a distinct etiopathogenesis of the mutations in keratinocytes occuring either during fetal development or in adult life.
CARBON EMISSION ACCOUNTING IN MRIO MODELS: THE TERRITORY VS. THE RESIDENCE PRINCIPLE

Consumption-based CO2 emissions, which are commonly calculated by means of environmentally extended input–output analysis, are gaining wider recognition as a way to complement territorial emission inventories. Although their use has increased significantly in the last years, insufficient attention has been paid to the methodological soundness of the underlying environmental extension. This should follow the internationally agreed accounting rules of the System of Environmental-Economic Accounting, which addresses the activities undertaken by the residents of a country, independent from where these take place. Nonetheless, some footprint calculations use extensions that account for all the activities within the territory, which leads to methodological inconsistencies. Thus, this article introduces the most relevant conceptual differences between these accounting frameworks and shows the magnitude of the gap between them building on the data generated for the EXIOBASE model. It concludes that the differences are high for many countries and their magnitude is increasing over time.