Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions

We evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of divrse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptognic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three‐dimensional data not available from conventional analysis.
Serial Changes in Diffusion Tensor Imaging Metrics of Corpus Callosum in Moderate Traumatic Brain Injury Patients and Their Correlation With Neuropsychometric Tests: A 2‐Year Follow‐up Study

ObjectiveTo assess longitudinally the severity of diffuse axonal injury in the corpus callosum in patients with moderate traumatic brain injury (TBI) through quantitative diffusion tensor imaging and to correlate these changes with neuropsychometric tests (NPT) at 6 and 24 months after injury. DesignProspective longitudinal study. ParticipantsSixteen patients with TBI and 17 age/sex-matched healthy controls. MethodsPatients underwent magnetic resonance imaging at 3 time points: within 2 weeks (range = 5–14 days), 6 months, and 24 months after injury. NPT could be performed only at 6 and 24 months. ResultsIn patients with TBI, a significant increase in fractional anisotropy (FA) values in genu as well as an insignificant decrease in radial diffusivity (RD) and mean diffusivity values in genu and splenium were observed over time, respectively. FA, RD, and mean diffusivity values continued to be abnormal in patients compared with controls at the end of 2 years. Although some NPT scores improved over time in these patients, these were still significantly impaired compared with controls. ConclusionsFA and RD indices appear to be surrogate markers of microstructural alterations in patients over time and correlate significantly with some of the NPT scores. The recovery in these indices associated with recovery in neurocognitive deficits suggests that these indices may be used as an objective marker for residual injury in these patients.
Short term testosterone replacement therapy improves libido and body composition.

OBJECTIVE To assess the efficacy and safety of testosterone replacement in males with late-onset hypogonadism compared to hypogonadal men without replacement, and controls, during six months. METHODS We assessed, through ADAM, AMS, IIEF-5 and SF-36 questionnaires, and through clinical and laboratory examinations, 62 patients divided into three groups: 17 hypogonadal males (HR) used intramuscular testosterone every three weeks; 14 hypogonadal males (HV) and 31 non-hypogonadal males (CV) used oral vitamins daily. RESULTS When compared to others, HR group obtained libido improvement assessed by ADAM 1 (p = 0.004), and borderline sexual potency improvement assessed by IIEF-5 (p = 0.053), besides a decrease in waist circumference after eight weeks (p = 0.018). The remaining parameters did not differ between the groups. PSA and hematocrit remained stable in those using testosterone. CONCLUSION Six months of testosterone replacement improved sexuality and body composition, with prostatic and hematological safety.
Matrix metalloproteinases and their inhibitors in aqueous humor of patients with pseudoexfoliation syndrome/glaucoma and primary open-angle glaucoma.

PURPOSE To determine the presence, activity, and quantitative differences of matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in aqueous humor and serum samples of patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma (PEXG), primary open-angle glaucoma (POAG), and cataract. METHODS Aqueous humor and serum samples were collected from 100 patients with PEX syndrome, PEX glaucoma (PEXG), POAG, and cataract, respectively. Levels of MMP-1, -2, -3, -7, -9, and -12 and TIMP-1 and -2 were determined by zymography, Western blot analysis, and specific immunoassays. Activity assay kits were used to quantitate levels of endogenously activated MMP-2 and -9. RESULTS MMP-2, -3, -7, -9, and -12 and TIMP-1 and -2 were identified in human aqueous humor samples from all groups of patients with a six to sevenfold molar excess of TIMPs over MMPs. Whereas serum samples showed no significant differences, total MMP-2 and -3 and TIMP-1 and -2 were detected at significantly higher concentrations in aqueous samples from PEX eyes with and without glaucoma compared with cataractous eyes. MMP-2 and -3 and TIMP-1 were also detected in higher, but not significantly different, amounts in aqueous samples of POAG eyes. However, levels of endogenously activated MMP-2 were significantly decreased in both PEX and POAG samples. The ratio of MMP-2 to its principal inhibitor TIMP-2 was balanced in cataract samples, but was decreased in samples from patients with PEXG, resulting in an excess of TIMP-2 over MMP-2. CONCLUSIONS The findings suggest that complex changes in the local MMP-TIMP balance and reduced MMP activity in aqueous humor may promote the abnormal matrix accumulation characteristic of PEX syndrome and may be causally involved in the pathogenesis of both PEX glaucoma and POAG.
Does Debt Diversification lead to a Discount in Firm Value?

Corporate firms access multiple sources of debt simultaneously. This study analyzes the impact of debt diversification on firm value. We argue that, when firms diversify their debt sources, the monitoring role played by debt holders decreases as a result of the free rider problem. Hence, such firms should experience a value discount in the capital markets. Our empirical analysis provides evidence for the existence of a value discount in the capital markets for firms accessing multiple sources of debt. Our results remain robust for alternative measures of debt diversification.
Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress

Mutations in the gene parkin in humans (PARK2) are responsible for a large number of familial cases of autosomal-recessive Parkinson disease. We have isolated a Drosophila homolog of human PARK2 and characterized its expression and null phenotype. parkin null flies have 30% lower mass than wild-type controls which is in part accounted for by a reduced cell size and number. In addition, these flies are infertile, show significantly reduced longevity, and are unable to jump or fly. Rearing mutants on paraquat, which generates toxic free radicals in vivo, causes a further reduction in longevity. Furthermore, loss of parkin results in progressive degeneration of most indirect flight muscle (IFM) groups soon after eclosion, accompanied by apoptosis. However, parkin mutants have normal neuromuscular junction recordings during the third larval instar stage, suggesting that larval musculature is intact and that parkin is required only in pupal and adult muscle. parkin flies do not show an age-dependent dopaminergic neuron loss in the brain, even after aging adults for 3 weeks. Nevertheless, degeneration of IFMs demonstrates the importance of parkin in maintaining specific cell groups, perhaps those with a high-energy demand and the concomitant production of high levels of free radicals. parkin mutants will be a valuable model for future analysis of the mechanisms of cell and tissue degeneration.
Constitutionalisation and Implementation of Devolution in Zimbabwe

In a unitary state devolution or decentralisation of power engenders the improvement of effectiveness and efficiency in governance as well as in the delivery of public services. Decentralisation entails the reduction of bureaucracy and the broadening of democratic space. It entails empowering stakeholders and communities to actively and effectively participate in decision-making on issues that affect them. As such it is widely courted as a means of enhancing good governance, which also fosters economic development general improvement in the living conditions and standards of communities’. In Zimbabwe, the debate on devolution has been intense and contentious, spanning the country’s nearly four decades of independence from British colonial rule. The current Zimbabwean constitution, which came into being 2013 provides for devolution of powers of government from central government to provincial, metropolitan and local authorities. Prior to this constitution, devolution was just a creature of statutes and power was predominantly centralised. The focus of this paper is to analyse the constitutional provisions as well as the dynamics attendant to its implementation. Lamentably, in spite of the constitutionalisation of devolution, it is yet to be implemented, more than five years after the establishment of the constitution, owing mainly to lack of political will, political conflict and weaknesses in the constitutional provisions themselves.
Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects.

BACKGROUND This study was designed to evaluate the effect of combining bupropion sustained release (SR) with venlafaxine, paroxetine, or fluoxetine in patients who reported unacceptable sexual dysfunction when treated with monotherapy with the latter 3 agents. METHOD Following a minimum of 6 weeks of antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI) or venlafaxine (a serotonin-norepinephrine reuptake inhibitor), eligible subjects received a further 8 weeks of monitored combination therapy with bupropion SR at a dose of 150 mg/day with no alterations to index antidepressant dosing. RESULTS There was a clinically significant benefit in 14 (78%) of 18 partial responders or nonresponders, and 33% (N = 6) achieved a full response (chi2= 8.06, df = 2, p = .017). Sexual dysfunction, particularly a decrease in orgasmic delay, was also significantly improved with combination therapy (men: paired t = -2.1, df = 6, p = .08; women: paired t = -3.0, df = 7, p = .02). Plasma monitoring of drugs and their metabolites revealed a statistically significant increase in venlafaxine levels (F = 6.89, df = 4,24; p = .001) accompanied by a decrease in O-desmethylvenlafaxine (F = 14.26; df = 4,24; p < .0005) during combined treatment with bupropion SR. There were no statistically significant changes in plasma levels of SSRIs (paroxetine and fluoxetine) during the trial. CONCLUSION Bupropion had an effect on the pharmacokinetics of venlafaxine but not those of the SSRIs. Further investigation of combination treatments under randomized, double-blind conditions is recommended.
Role of Intelligence Tests in Speech/Language Referrals

This study examined the relation of the WISC–R Verbal IQ with measures of oral and written language among 190 students referred to a private educational clinic over a 5-yr. period. Correlations of Verbal IQ with scores on measures of oral language, written language, receptive language, reading comprehension, and basic reading skills were calculated for the total sample and by Grades 1–3, 4–7, and 8–11. Standard regression coefficients were used to estimate the proportion of variance explained by these five measures. Significant correlations were found for Verbal IQ with the measures, ranging from . 36 (Basic Reading Skills) to . 69 (Receptive Vocabulary). Multiple regression indicated that 59% of the variance was explained by the five measures and that three—Oral Language, Receptive Vocabulary, and Reading Comprehension—contributed significantly to Verbal IQ. Correlations across grades showed inconsistent differences by grade for Verbal IQ with language variables. Implications for speech-language referral practices are discussed.
LINEARITY AND RELIABILITY OF THE IEMG V TORQUE RELATIONSHIP FOR THE FOREARM FLEXORS AND LEG EXTENSORS

The purpose of this investigation was to examine the linearity and reliability of the surface integrated electromyogram (IEMG) v isometric torque relationship for the leg extensors and forearm flexors. Nine men and four women (mean age ± SD=22 ± 2 yr) volunteered for this investigation. Isometric testing was conducted on a Cybex II isokinetic dynamometer with the lever arm at 0.785 rad (45° )below the horizontal plane for the leg extensors and in the vertical plane for the forearm flexors. Bipolar surface electrodes were used to record IEMG values from the vastus lateralis and biceps brachii. To examine test-retest reliability, two test sessions, separated by a minimum of 48 h, were performed. The test-retest linearity of the IEMG v torque relationship ranged from r2= 0.77 to 0.96 and 0.55 to 0.94 for the forearm flexors and r2=0.81 to 0.98 and 0.83 to 0.98 for the leg extensors. The slope values were not significantly different (P>0.05) between sessions and were correlated (intraclass correlation coefficients) at R=0.86 (standard error of estimate (SEE)=5.77 μV-Nm-1, 31% of the mean) and R=0.97 (SEE=0.27 μV-Nm-1, 12% of the mean) for the forearm flexors and leg extensors, respectively. The test-retest maximal torque values were 57.73 ± 22.57 Nm and 58.14 ± 2.81 Nm (R=0.99; SEE=2.39 Nm) for the forearm flexors and 187.79 ± 55.98 Nm and 195.42 ± 56.27 Nm (R=0.96; SEE=22.62 Nm) for the leg extensors (nonsignificant differences; P>0.05). Similarly, the test-retest maximal IEMG values were highly correlated (R=0.95 for forearm flexors and leg extensors) and not significantly different (P>0.05). The results indicated that the IEMG v torque relationship for the leg extensors exhibited better linearity and reliability than the forearm flexors. For both muscle groups, however, the maximal IEMG and torque values were highly reliable.
The oligopeptide DT‐2 is a specific PKG I inhibitor only in vitro, not in living cells

BACKGROUND AND PURPOSE cGMP is involved in the regulation of many cellular processes including cardiac and smooth muscle contractility, aldosterone synthesis and inhibition of platelet activation. Intracellular effects cGMP are mediated by cGMP‐dependent PKs, cGMP‐regulated PDEs and cGMP‐gated ion channels. PKG inhibitors are widely used to discriminate PKG‐specific effects. They can be divided into cyclic nucleotide‐binding site inhibitors such as Rp‐phosphorothioate analogues (Rp‐cGMPS), ATP‐binding site inhibitors such as KT5823, and substrate binding site inhibitors represented by the recently described DT‐oligopeptides. As it has been shown that Rp‐cGMPS and KT5823 have numerous non‐specific effects, we analysed the pharmacological properties of the oligopeptide (D)‐DT‐2 described as a highly specific, membrane–permeable, PKG inhibitor.
The Effects of a Mixed Approach Toward Management Earnings Forecasts: Evidence from China

Chinese regulators mandate management earnings forecasts when managersâ€™ earnings expectations meet brightâ€ line thresholds and allow voluntary forecasts in other circumstances. We examine the effects of this mixed approach. We find that Chinese mandatory forecasts have significant information content. Moreover, we observe a learning effect: mandatory forecasts appear to stimulate voluntary forecasts in subsequent periods as managers become familiar with the forecasting and disclosing procedures through forced experience. We find one negative consequence of the mixed approach, however: managers appear to manipulate earnings to avoid the forecast threshold of large earnings decreases. Overall, we document the pros and cons of a mixed approach toward management earnings forecasts in a major emerging market.
An Exploratory Study of Two Caco-2 Cell Models for Oral Absorption: A Report on Their Within-laboratory and Between-laboratory Variability, and Their Predictive Capacity

In 2005, the European Centre for the Validation of Alternative Methods (ECVAM) sponsored a study aimed at evaluating the reproducibility (between-laboratory and within-laboratory variability) and the predictive capacity of two in vitro cellular systems — the Caco-2/ATCC parental cell line and the Caco-2/TC7 clone — for estimating the oral fraction absorbed (Fa) in humans. Two laboratories, both of which had experience with Caco-2 cultures, participated in the study. Ten test chemicals with documented in vivo oral absorption data were selected. Atenolol, cimetidine and propranolol were included as reference compounds for low, medium and high intestinal absorption, respectively. Transport experiments were independently carried out in the two laboratories, according to an agreed protocol. The apparent permeability coefficient (Papp) was calculated in either the apical to basolateral (absorption) or the basolateral to apical (efflux) direction. To investigate the involvement of possible active transport processes, experiments were also performed in the presence of sodium azide plus 2-deoxy-D-glucose in the donor compartment. Before performing the permeability experiments, the highest concentration that did not impair barrier integrity was identified for each test chemical in both cell models, by applying the chemicals together with a marker of the paracellular pathway. In addition, barrier integrity was assessed by measuring the trans-epithelial electrical resistance. All the permeability data obtained were independently analysed. Reproducibility was assessed for the seven substances for which sufficient data were available. Within-laboratory variability was based on coefficient of variation (CV) values. Median CV values of 10.4% and 14.7% were found for the two laboratories. Concerning between-laboratory reproducibility, comparable response levels were obtained for the three reference compounds and for paracetamol, while, for the other chemicals, the results were less reproducible — in particular, for compounds known to be actively transported. The Papp values obtained for both cell lines were comparable for identical experimental conditions. Despite the limited number of substances tested, the predictive capacity was investigated by using two mathematical models available in the literature. Good estimations of the human Fa were obtained for five well-absorbed compounds, while moderately and poorly absorbed compounds were overestimated. It is proposed that a confirmatory study addressing the main results, including power considerations, would now be useful.
CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses1

Specific and selective immunological unresponsiveness to donor alloantigens can be induced in vivo. We have shown previously that CD25+CD4+ T cells from mice exhibiting long-term operational tolerance to donor alloantigens can regulate rejection of allogeneic skin grafts mediated by CD45RBhighCD4+ T cells. In this study, we wished to determine whether donor-specific regulatory cells can be generated during the induction phase of unresponsiveness, i.e., before transplantation. We provide evidence that pretreatment with anti-CD4 Ab plus a donor-specific transfusion generates donor-specific regulatory CD25+CD4+ T cells that can suppress rejection of skin grafts mediated by naive CD45RBhighCD4+ T cells. Regulatory cells were contained only in the CD25+ fraction, as equivalent numbers of CD25−CD4+ T cells were unable to regulate rejection. This pretreatment strategy led to increased expression of CD122 by the CD25+CD4+ T cells. Blockade of both the IL-10 and CTLA-4 pathways abrogated immunoregulation mediated by CD25+ T cells, suggesting that IL-10 and CTLA-4 are required for the functional activity of this population of immunoregulatory T cells. In clinical transplantation, the generation of regulatory T cells that could provide dynamic control of rejection responses is a possible route to permanent graft survival without the need for long-term immunosuppression.
Evolutionary Origins of a Bioactive Peptide Buried within Preproalbumin[C][W]

A dual biosynthesis that produces seed albumin and a protease-inhibiting peptide in sunflower was found to have evolved over 18 million years ago and has spawned a family of peptides diverse in sequence and three-dimensional structure. Using the gene sequences and an understanding of the peptide biosynthesis, the biochemical steps that allowed these buried peptides to evolve de novo were proposed. The de novo evolution of proteins is now considered a frequented route for biological innovation, but the genetic and biochemical processes that lead to each newly created protein are often poorly documented. The common sunflower (Helianthus annuus) contains the unusual gene PawS1 (Preproalbumin with SFTI-1) that encodes a precursor for seed storage albumin; however, in a region usually discarded during albumin maturation, its sequence is matured into SFTI-1, a protease-inhibiting cyclic peptide with a motif homologous to unrelated inhibitors from legumes, cereals, and frogs. To understand how PawS1 acquired this additional peptide with novel biochemical functionality, we cloned PawS1 genes and showed that this dual destiny is over 18 million years old. This new family of mostly backbone-cyclic peptides is structurally diverse, but the protease-inhibitory motif was restricted to peptides from sunflower and close relatives from its subtribe. We describe a widely distributed, potential evolutionary intermediate PawS-Like1 (PawL1), which is matured into storage albumin, but makes no stable peptide despite possessing residues essential for processing and cyclization from within PawS1. Using sequences we cloned, we retrodict the likely stepwise creation of PawS1’s additional destiny within a simple albumin precursor. We propose that relaxed selection enabled SFTI-1 to evolve its inhibitor function by converging upon a successful sequence and structure.
Development of Fatal Colitis in FVB Mice Infected with Citrobacter rodentium

ABSTRACT Citrobacter rodentium is the causative agent of transmissible murine colonic hyperplasia. The disease is characterized by severe but temporary epithelial hyperplasia with limited inflammation in the descending colon of adult mice on a variety of genetic backgrounds. The natural history of infection with this murine pathogen has been characterized in outbred Swiss Webster (SW) mice but not in the cognate inbred FVB strain. In contrast to subclinical infection in SW mice, 12-week-old FVB mice developed overt disease with significant weight loss and mortality beginning by 9 days postinoculation (dpi). By 21 dpi, more than 75% of infected FVB mice died or had to be euthanized, whereas no mortality developed in SW mice. Mortality in FVB mice was fully prevented by fluid therapy. Fecal shedding of bacteria was similar in both groups through 9 dpi; however, a slight but significant delay in bacterial clearance was observed in FVB mice by 12 to 18 dpi. SW mice developed hyperplasia with minimal inflammation in the descending colon. FVB mice developed epithelial cell hyperproliferation, severe inflammation with erosions and ulcers, and epithelial atypia by 6 dpi in the descending colon. In the majority of surviving FVB mice, colonic lesions, including epithelial atypia, were reversible, although a small percentage (5 to 7%) exhibited chronic colitis through 7 months postinoculation. The existence of susceptible and resistant lines of mice with similar genetic backgrounds will facilitate the identification of host factors responsible for the outcome of infection and may lead to the development of novel strategies for preventing and treating infectious colitis.