Miracle-dz/UniFAR-FTUs huggingface dataset:
Morphological Patterns of Seizures Recorded Intracranially

Summary: We analyzed the frequency and morphological characteristics of the initial EEG manifestations of spontaneous seizures recorded from depth and subdural electrodes in 26patients for whom pathological analysis of the area of seizure onset was available after resective surgery. Pathological features considered to be positive findings included well‐defined structural lesions (hamartoma, neoplasm) or strictly defined mesial temporal sclerosis. Seizure onset was characterized by the frequency of the rhythmic discharge >2 Hz in the first second and by the presence or absence of periodic low‐frequency spikes (<2 Hz) preceding this stable change in background frequency. These features were correlated with the presence or absence of pathologic abnormalities in temporal and extratemporal locations. Although all patterns and frequencies of seizure onset were recorded in both medial temporal and extratemporal locations, medial temporal seizure onset was significantly more likely to have high frequency (>13 Hz, p < 0.05) and no periodic spikes before seizure onset tended to periodic spikes prior to the seizure when it was associated with medial temporal sclerosis compared to when it was not. Extratemporal seizure onset associated with abnormal pathological substrate was significantly more likely to have a lower frequency (<13 Hz, p < 0.05) and no periodic spikes before seizure onset (p < 0.00001) than extratemporal seizure onset recorded from areas without pathological findings. Variability of seizure onset frequency was a characteristic of temporal, but not extra temporal, seizures (p < 0.01). The existence of such differences between seizures of temporal and extratemporal origin suggests that the underlying anatomy may in part determine these patterns, and that interpretation of EEG records of seizures beginning in different cerebral locations requires recognition of these differences.
Risk of Renal Scarring in Children With a First Urinary Tract Infection: A Systematic Review

BACKGROUND: To our knowledge, the risk of renal scarring in children with a urinary tract infection (UTI) has not been systematically studied. OBJECTIVE: To review the prevalence of acute and chronic renal imaging abnormalities in children after an initial UTI. METHODS: We searched Medline and Embase for English-, French-, and Spanish-language articles using the following terms: “Technetium 99mTc dimercaptosuccinic acid (DMSA),” “DMSA,” “dimercaptosuccinic,” “scintigra*,” “pyelonephritis,” and “urinary tract infection. ” We included articles if they reported data on the prevalence of abnormalities on acute-phase (≤15 days) or follow-up (>5 months) DMSA renal scans in children aged 0 to 18 years after an initial UTI. Two evaluators independently reviewed data from each article. RESULTS: Of 1533 articles found by the search strategy, 325 full-text articles were reviewed; 33 studies met all inclusion criteria. Among children with an initial episode of UTI, 57% (95% confidence interval [CI]: 50–64) had changes consistent with acute pyelonephritis on the acute-phase DMSA renal scan and 15% (95% CI: 11–18) had evidence of renal scarring on the follow-up DMSA scan. Children with vesicoureteral reflux (VUR) were significantly more likely to develop pyelonephritis (relative risk [RR]: 1.5 [95% CI: 1.1–1.9]) and renal scarring (RR: 2.6 [95% CI: 1.7–3.9]) compared with children with no VUR. Children with VUR grades III or higher were more likely to develop scarring than children with lower grades of VUR (RR: 2.1 [95% CI: 1.4–3.2]). CONCLUSIONS: The pooled prevalence values provided from this study provide a basis for an evidence-based approach to the management of children with this frequently occurring condition.
Innate Immunity to Viruses: Control of Vaccinia Virus Infection by γδ T Cells1

The existence of γδ T cells has been known for over 15 years, but their significance in innate immunity to virus infections has not been determined. We show here that γδ T cells are well suited to provide a rapid response to virus infection and demonstrate their role in innate resistance to vaccinia virus (VV) infection in both normal C57BL/6 and β TCR knockout (KO) mice. VV-infected mice deficient in γδ T cells had significantly higher VV titers early postinfection (PI) and increased mortality when compared with control mice. There was a rapid and profound VV-induced increase in IFN-γ-producing γδ T cells in the peritoneal cavity and spleen of VV-infected mice beginning as early as day 2 PI. This rapid response occurred in the absence of priming, as there was constitutively a significant frequency of VV-specific γδ T cells in the spleen in uninfected β TCR KO mice, as demonstrated by limiting dilution assay. Also, like NK cells, another mediator of innate immunity to viruses, γδ T cells in uninfected β TCR KO mice expressed constitutive cytolytic activity. This cytotoxicity was enhanced and included a broader range of targets after VV infection. VV-infected β TCR KO mice cleared most of the virus by day 8 PI, the peak of the γδ T cell response, but thereafter the γδ T cell number declined and the virus recrudesced. Thus, γδ T cells can be mediators of innate immunity to viruses, having a significant impact on virus replication early in infection in the presence or absence of the adaptive immune response.
Effect of the hypotensive drug ST 155 (Catapres) on the heart and peripheral circulation.

The action of the recently developed hypotensive drug ST 155 (Catapres) on the heart and peripheral circulation has been investigated. The intravenous injection of 5 µg/kg of ST 155 into rabbits and dogs caused bradycardia and a biphasic change in arterial blood pressure, characterized by an initial transient pressor response followed by a sustained fall. The initial pressor response was prolonged and often potentiated after pretreatment with either pentolinium tartrate, bnetylium tosylate, reserpine or atropine and after the spinal cord had been transected at C1-2 or C2-3. Both phases of the blood pressure response were modified by phenoxybenzamine. Left ventricular workfunction curves indicated that 5 µg/kg of ST 155 caused a small but significant decrease in left ventricular function during conditions of high, but not under conditions of low, load. It did, however, consistently produce bradycardia. The continuous intravenous infusion of 1.0 µg/kg/min of ST 155 into rabbits resulted in a fall in blood pressure, without any initial pressor response. The similar infusion of ST 155 after reserpine pretreatment resulted in a prolonged pressor response which was antagonized by phenoxybenzamine. Dose-response studies in dogs provided two nonconvergent dose-response curves, one relating to the pressor effect and the other to the fall in blood pressure. Cardiac output in rabbits and dogs was reduced after ST 155. This reduction in cardiac output may be related to the systemic venodilation caused by ST 155 and hence to a decrease in venous return to the heart. These results are discussed in accordance with the hypothesis that the initial pressor effect of ST 155 results from stimulation of alpha adrenergic receptors and that the hypotensive response involves the central inhibition of an adrenergic mechanism mediating constriction.
Topical Review on Epigenetics and Chromatin Modifications Epigenetics: Beyond Chromatin Modifications and Complex Genetic Regulation

Chromatin modifications and epigenetics may play important roles in many plant processes, including developmental regulation, responses to environmental stimuli, and local adaptation. Chromatin modifications describe biochemical changes to chromatin state, such as alterations in the specific type or placement of histones, modifications of DNA or histones, or changes in the specific proteins or RNAs that associate with a genomic region. The term epigenetic is often used to describe a variety of unexpected patterns of gene regulation or inheritance. Here, we specifically define epigenetics to include the key aspects of heritability (stable transmission of gene expression states through mitotic or meiotic cell divisions) and independence from DNA sequence changes. We argue against generically equating chromatin and epigenetics; although many examples of epigenetics involve chromatin changes, those chromatin changes are not always heritable or may be influenced by genetic changes. Careful use of the terms chromatin modifications and epigenetics can help separate the biochemical mechanisms of regulation from the inheritance patterns of altered chromatin states. Here, we also highlight examples in which chromatin modifications and epigenetics affect important plant processes.
Metabolic Alterations in Two Cirsium Species Identified at Distinct Phenological Stages using UPLC-QTOF/MS.

INTRODUCTION Cirsium chanroenicum and C. setidens are commonly used both in traditional folk medicine and as a food source. The quality of different species of Cirsium at different harvest times is a function of their metabolite composition, which is determined by the phenological stage. OBJECTIVE We sought to determine the differences in the metabolite composition of two species of Cirsium during different phenological stages using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight (QTOF) mass spectrometry (MS). METHODOLOGY Cirsium chanroenicum and C. setidens plants were collected at the floral budding and full flowering stages. Metabolic profiles of Cirsium extracts were determined using UPLC-QTOF/MS to characterise the differences between phenological stages, and the major metabolites were quantified using UPLC-QTOF/MS-multiple reaction monitoring (MRM). RESULTS At the full flowering stage, the levels of phenolic acids as well as components of the phenylpropanoid pathway were increased. Flavonoids predominated at the full flowering stage in both species. The levels of coumaric acid, kaempferol, and pectolinarigenin differed between the two species of Cirsium. Overall, these results suggest that components of the phenylpropanoid metabolic pathway are upregulated in the full flowering stage in Cirsium, although we did observe some variation between the species. CONCLUSION These results will help elucidate the metabolic pathways related to the different phases of the vegetative cycle, and may help determine the optimal season for the harvest of Cirsium with the highest levels of bioactive compounds. Copyright © 2017 John Wiley & Sons, Ltd.
How patient cost-sharing trends affect adherence and outcomes: a literature review.

OBJECTIVE We sought to assess the relationship between patient cost sharing; medication adherence; and clinical, utilization, and economic outcomes. METHODOLOGY We conducted a literature review of articles and abstracts published from January 1974 to May 2008. Articles were identified using PubMed, Ovid, medline, Web of Science, and Google Scholar databases. The following terms were used in the search: adherence, compliance, copay, cost sharing, costs, noncompliance, outcomes, hospitalization, utilization, economics, income, and persistence. RESULTS We identified and included 160 articles in the review. Although the types of interventions, measures, and populations studied varied widely, we were able to identify relatively clear relationships between cost sharing, adherence, and outcomes. Of the articles that evaluated the relationship between changes in cost sharing and adherence, 85% showed that an increasing patient share of medication costs was significantly associated with a decrease in adherence. For articles that investigated the relationship between adherence and outcomes, the majority noted that increased adherence was associated with a statistically significant improvement in outcomes. CONCLUSION Increasing patient cost sharing was associated with declines in medication adherence, which in turn was associated with poorer health outcomes.
A Robust Set-Valued Scenario Approach for Handling Modeling Risk in Portfolio Optimization

For portfolio optimization under downside risk measures, such as conditional value-at-risk or lower partial moments, we often invoke a scenario approach to approximate the high-dimensional integral involved when calculating risk. Consequently, two types of modeling risk may arise from this procedure: uncertainty in determining the distribution of asset returns and the error caused by approximating a given distribution with scenarios. To handle these two types of modeling risk within a unified framework, we propose a mathematically tractable set-valued scenario approach. More specifically, when short selling is not permitted, the robust portfolio selection problems modeled within a minimum-maximum decision framework using several types of set-valued scenarios can be translated into linear programs or second-order cone programs. These can be efficiently solved by the interior point method. The proposed set-valued scenario approach can be used not only as a methodology to alleviate the modeling risk but also as a useful tool for evaluating the impact of modeling risk. Our simulation analysis and empirical study show that robustness does not necessarily imply conservativeness, portfolio performance is affected by the investment style characterized by the return-risk tradeoff to a large degree and modeling risk only becomes significant when an aggressive strategy is adopted.
Ultraviolet-B-induced erythema is mediated by nitric oxide and prostaglandin E2 in combination.

Ultraviolet-B-induced erythema (one, two, or four times the minimal erythema dose) was reduced but not abolished by application of 1% indomethacin gel immediately after irradiation of human skin. Continuous synthesis of prostaglandins is reflected by similar levels of indomethacin-mediated inhibition of erythema at any time within 48 h after irradiation. Repeated applications of indomethacin did not increase the inhibition. Twenty-four hours after irradiation with four minimal erythema doses, mean prostaglandin E2 levels in suction blisters were 27.2 ng per ml (SEM 11) compared with 8.6 ng per ml in unirradiated skin (n = 25; p < 0.01). Prosta glandin E2 levels in dermal tissues, sampled by microdialysis (depth 0.6 +/- 0.1 mm), were 310 pg per ml (SEM 123) and 237 pg per ml (SEM 88) in irradiated and unirradiated skin, respectively (n = 7, n.s.). Nitric oxide also made a significant contribution to ultraviolet-B-induced erythema. Ultraviolet erythema was inhibited by L-NAME in a dose-related fashion with 2 mM L-NAME causing total abolition of the response. L-NAME was effective at all time points up to 48 h suggesting that NO was produced continuously. NO was undetectable in suction blister fluid but in dermal microdialysate NO was present at 44.3 ng per ml (SEM 6.2) following ultraviolet B compared with 26.0 ng per ml (SEM 8.0) in unirradiated skin (p < 0.05), approximately 1000 times the molar concentration of prostaglandin E2. These findings confirm prostaglandin E2 and NO to be mediators of ultraviolet-induced erythema. They also show that there is prolonged synthesis of both mediators within the erythemal response and that synthesis of NO is induced by lower doses of ultraviolet B compared with that of prostaglandin E2.
Zonulae adherentes pore size in the external limiting membrane of the rabbit retina.

The interphotoreceptor space (IPS) of the retina is bordered by the retinal pigment epithelium, photoreceptors, and Müller cells and surrounds the photoreceptor outer and inner segments. It contains a matrix composed of glycosaminoglycans and proteins, including interphotoreceptor retinol-binding protein (IRBP). The matrix does not diffuse sclerad through the tight junctions that link cells of the pigment epithelium or vitread beyond the point at which photoreceptors and Müller cells are linked by zonulae adherentes that comprise the external limiting membrane (ELM). Biotinylated protein probes of known Stokes' radius were used to determine the pore size of the ELM. Following exposure of the photoreceptor side of isolated rabbit retinas to each protein, the extent of diffusion of the probe through the retina was determined by avidin D-horseradish peroxidase histochemistry. Each protein with a Stokes' radius of 30 A or less diffused freely through the neurosensory retina while each protein with a Stokes' radius greater than 36 A was blocked abruptly at the ELM. Thus, the pore radius of the zonulae adherentes of the ELM lies between 30 and 36 A, which is sufficiently small to account for containment of IRBP (55 A) within the IPS. This study emphasizes that in addition to providing structural support, the zonulae adherentes of the ELM serve to define an important extracellular space of the retina. This has clinical relevance, since two serum proteins tested, albumin and gamma-globulin, are too large to diffuse through an intact ELM. This may explain why protein-rich fluid accumulates in the IPS when the outer blood retinal barrier is compromised by disease or injury. (ABSTRACT TRUNCATED AT 250 WORDS)
Exochelin genes in Mycobacterium smegmatis: identification of an ABC transporter and two non‐ribosomal peptide synthetase genes

Many strains of mycobacteria produce two ferric chelating substances that are termed exochelin (an excreted product) and mycobactin (a cell‐associated product). These agents may function as iron acquisition siderophores. To examine the genetics of the iron acquisition system in mycobacteria, ultraviolet (UV) and transposon (Tn611 ) mutagenesis techniques were used to generate exochelin‐deficient mutants of Mycobacterium smegmatis strains ATCC 607 and LR222 respectively. Mutants were identified on CAS siderophore detection agar plates. Comparisons of the amounts of CAS‐reactive material excreted by the possible mutant strains with that of the wild‐type strains verified that seven UV mutant strains and two confirmed transposition mutant strains were deficient in exochelin production. Cell‐associated mycobactin production in the mutants appeared to be normal. From the two transposon mutants, the mutated gene regions were cloned and identified by colony hybridization with an IS6100 probe, and the DNA regions flanking the transposon insertion sites were then used as probes to clone the wild‐type loci from M. smegmatis LR222 genomic DNA. Complementation assays showed that an 8 kb Pst I fragment and a 4.8 kb Pst I/SacI subclone of this fragment complemented one transposon mutant (LUN2) and one UV mutant (R92). A 10.1 kb SacI fragment restored exochelin production to the other transposon mutant (LUN1). The nucleotide sequence of the 15.3 kb DNA region that spanned the two transposon insertion sites overlapped the 5′ region of the previously reported exochelin biosynthetic gene fxbA and contained three open reading frames that were transcribed in the opposite orientation to fxbA. The corresponding genes were designated exiT, fxbB and fxbC. The deduced amino acid sequence of ExiT suggested that it was a member of the ABC transporter superfamily, while FxbB and FxbC displayed significant homology with many enzymes (including pristinamycin I synthetase) that catalyse non‐ribosomal peptide synthesis. We propose that the peptide backbone of the siderophore exochelin is synthesized in part by enzymes resembling non‐ribosomal peptide synthetases and that the ABC transporter ExiT is responsible for exochelin excretion.
Analysis of body regions and components of PASI scores during adalimumab or methotrexate treatment for patients with moderate-to-severe psoriasis.

BACKGROUND The PASI score, the most common outcome measure in clinical trials of psoriasis treatment, is a non-linear scale that does not allow reliable assessment of subtle variations of its components (erythema, induration, and desquamation). OBJECTIVE Highlight treatment response patterns potentially hidden by PASI score's compounded weighted-average calculation. METHODS Patients with moderate-to-severe psoriasis enrolled in the phase-3, 16-week, randomized CHAMPION study, and received adalimumab, methotrexate, or placebo. PASI scores were assessed post hoc for improvement, by body region and component. RESULTS At Week 16, a significantly greater percentage of adalimumab-treated patients vs methotrexate- and placebo-treated patients, achieved PASI 75, PASI 90 and PASI 100 response in each body region and component. 55.7% of adalimumab-treated patients reached PASI 100 response in the head and neck region vs 16.7% overall. Two key components of PASI, induration and desquamation, were affected by treatment more than erythema, the third component. Adalimumab was particularly effective in complete resolution of induration (44.9% of patients) vs methotrexate (10.9%). For all PASI body regions and components, mean percent improvement in score at Weeks 2, 4, 8, 12, and 16 was significantly greater (P<0.05) for adalimumab treatment vs methotrexate or placebo. CONCLUSION Adalimumab therapy resulted in complete resolution of individual body regions in at least 30.6% up to 55.7% of patients in CHAMPION. This was more than twice that of methotrexate and placebo. PASI improvement by body region is a novel and an important patient-relevant outcome worthy of reporting in future studies.
Dual kidney transplantation from uncontrolled deceased donors after cardiac arrest: A possible option

Organ shortage is a major problem in organ transplantation. For this reason, transplantation teams have found it necessary to revisit their organ acceptance criteria. Uncontrolled deceased donors after cardiac arrest could increase the donor pool by 20%, but at the same time there is a greater risk of delayed graft function and primary non‐function. Dual kidney transplantation is an option when single kidney transplantation cannot be carried out because of lack of organ quality. We report for the first time our four first dual kidney transplantation from uncontrolled deceased donors after cardiac arrest with a follow up longer than 1 year. We described graft outcomes until 5 years, and histology at 3 and 12 months after transplantation. All organs were machine perfused in order to assess their quality leading to a single kidney transplantation or dual kidney transplantation decision. After 1 year of follow up, all grafts were functional with a mean estimated glomerular filtration rate of 44.5 ± 3.3 mL/min/1.73 m2, and a mean inulin clearance of 43.7 ± 13.6 mL/mn/1.73 m2. These findings suggest that dual kidney transplantation can represent a viable option for kidneys unsuitable for single kidney transplantation without increasing the rate of surgical complications. Successful transplantation is linked to histological, biological and donor clinical criteria, as well as perfusion parameters.