Miracle-dz/UniFAR-FTUs huggingface dataset:
[De novo cerebral aneurysms].

OBJECTIVE To substantiate the reasonability and duration of angiographic follow-up of patients operated on for cerebral aneurysms to rule out de novo aneurysm formation. MATERIAL AND METHODS The results of angiographic examination (cerebral angiography and SCT angiography) of 43 patients with cerebral aneurysms operated on at the Burdenko Neurosurgical Institute in 1995-2012 are analyzed. The follow-up duration varied from 1 to 14 years after surgery (mean duration, 5 years). Patients' age ranged from 14 to 56 years. RESULTS Control angiographic examination showed that de novo aneurysms were formed in 7 (16.2%) patients. A total of 8 de novo aneurysms were detected (in one case there were two aneurysms formed). All aneurysms, both the previously operated and the de novo ones, were located in the anterior part of the circle of Willis. De novo aneurysms were clipped in 5 cases; the cavity of the de novo aneurysm was occluded with spirals in one case. One patient with a small aneurysm of the middle cerebral artery refused surgery. Neither lethal nor unfavorable outcomes were recorded. CONCLUSIONS The patient groups with the high risk of de novo aneurysm formation are as follows: 1) young smokers with hypertension; 2) patients who developed clinical signs of the disease when being young; 3) patients subjected to proximal exclusion of the main artery; and 4) patients with multiple and familial forms of the pathology. Dynamic angiographic follow-up (SCT angiography or magnetic resonance angiography) for 1-3 years is recommended for these patients.
Abnormal Chondrocyte Apoptosis in the Cartilage Growth Plate is Influenced by Genetic Background and Deletion of CHOP in a Targeted Mouse Model of Pseudoachondroplasia

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by mutations in cartilage oligomeric matrix protein (COMP) and characterised by short limbed dwarfism and early onset osteoarthritis. Mouse models of PSACH show variable retention of mutant COMP in the ER of chondrocytes, however, in each case a different stress pathway is activated and the underlying disease mechanisms remain largely unknown. T585M COMP mutant mice are a model of moderate PSACH and demonstrate a mild ER stress response. Although mutant COMP is not retained in significant quantities within the ER of chondrocytes, both BiP and the pro-apoptotic ER stress-related transcription factor CHOP are mildly elevated, whilst bcl-2 levels are decreased, resulting in increased and spatially dysregulated chondrocyte apoptosis. To determine whether the abnormal chondrocyte apoptosis observed in the growth plate of mutant mice is CHOP-mediated, we bred T585M COMP mutant mice with CHOP-null mice to homozygosity, and analysed the resulting phenotype. Although abnormal apoptosis was alleviated in the resting zone following CHOP deletion, the mutant growth plates were generally more disorganised. Furthermore, the bone lengths of COMP mutant CHOP null mice were significantly shorter at 9 weeks of age when compared to the COMP mutant mice, including a significant difference in the skull length. Overall, these data demonstrate that CHOP-mediated apoptosis is an early event in the pathobiology of PSACH and suggest that the lack of CHOP, in conjunction with a COMP mutation, may lead to aggravation of the skeletal phenotype via a potentially synergistic effect on endochondral ossification.
Probing morphological, syntactic and pragmatic knowledge through answers to wh-questions in children with SLI

Abstract Purpose: This study investigated aspects of morphology, syntax and pragmatics in children with Specific Language Impairment (SLI). These areas of language were investigated by evaluating children’s answers to wh-questions. Method: Elicited production methodology was used to evoke answers to three types of wh-questions. There were 54 participants: 18 children with SLI (mean age = 5;3); 18 language-matched children matched on mean length of utterance (mean age = 3;4) and 18 age-matched children (mean age = 5;3). Result: The SLI group demonstrated comprehension of the wh-questions, as revealed by their answers using the appropriate syntactic category. Children with SLI also demonstrated knowledge of pragmatics by using a pronoun to refer to a discourse referent that was previously introduced as a full noun phrase. Unlike the control children, children with SLI did not show sensitivity to one measure of the Maxim of Quantity; they gave more full sentence answers to wh-questions in contexts when most speakers would give a shorter, fragment answer. The tense-related morphology was also frequently omitted from children’s answers. Conclusion: The experiment revealed that children with SLI did well on syntactic and pragmatic measures. The greatest challenge was in providing tense-related morphemes in their answers to questions.
Predicting the knowledge–recklessness distinction in the human brain

Significance Because criminal statutes demand it, juries often must assess criminal intent by determining which of two legally defined mental states a defendant was in when committing a crime. For instance, did the defendant know he was carrying drugs, or was he merely aware of a risk that he was? Legal scholars have debated whether that conceptual distinction, drawn by law, mapped meaningfully onto any psychological reality. This study uses neuroimaging and machine-learning techniques to reveal different brain activities correlated with these two mental states. Moreover, the study provides a proof of principle that brain imaging can determine, with high accuracy, on which side of a legally defined boundary a person's mental state lies. Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria. We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those risks possessed by the participants. Our results provide neural evidence of a detectable difference in the mental state of knowledge in contrast to recklessness and suggest, as a proof of principle, the possibility of inferring from brain data in which legally relevant category a person belongs. Some potential legal implications of this result are discussed.
The Impact of Recovery of Visuo-Spatial Neglect on Motor Recovery of the Upper Paretic Limb after Stroke

The aim of the current study was to investigate the longitudinal relationship between improvements of synergism and strength of the upper paretic limb and severity of visuo-spatial neglect during the first 52 weeks post-stroke. The longitudinal association between severity of VSN and motor impairment using Fugl Meyer motor score and Motricity Index of the arm was measured in an intensive repeated measurement design including 18 measurement sessions for each subject. Neglect was assessed using the letter cancellation test applied in a prospective cohort of 101 ischemic, first-ever, hemispheric stroke patients. All time-dependent measures were taken weekly, starting within 14 days post-stroke. From week 10 to 20 biweekly measurements are obtained. The longitudinal relationship of (bi)weekly time on improvement of motor functions and severity of neglect was investigated using random coefficient analysis and trend analyses. Fifty-one of the 101 stroke patients showed neglect at stroke onset. Less improvement of synergism and strength of the upper paretic limb was associated with more severe neglect. This association was most pronounced in the first 10 weeks post-stroke. The seemingly suppressive effect of neglect on upper-limb motor recovery appears to take place mainly during spontaneous neurological recovery of first 10 weeks post-stroke. This finding suggests that damage to large-scale white matter tracts of especially the perceptual-attention networks suppress recovery of other networks at distance in the brain suggesting a common underlying mechanism.
Overexpression of OsMYB48-1, a Novel MYB-Related Transcription Factor, Enhances Drought and Salinity Tolerance in Rice

MYB-type transcription factors (TFs) play essential roles in plant growth, development and respond to environmental stresses. Role of MYB-related TFs of rice in drought stress tolerance is not well documented. Here, we report the isolation and characterization of a novel MYB-related TF, OsMYB48-1, of rice. Expression of OsMYB48-1 was strongly induced by polyethylene glycol (PEG), abscisic acid (ABA), H2O2, and dehydration, while being slightly induced by high salinity and cold treatment. The OsMYB48-1 protein was localized in the nucleus with transactivation activity at the C terminus. Overexpression of OsMYB48-1 in rice significantly improved tolerance to simulated drought and salinity stresses caused by mannitol, PEG, and NaCl, respectively, and drought stress was caused by drying the soil. In contrast to wild type plants, the overexpression lines exhibited reduced rate of water loss, lower malondialdehyde (MDA) content and higher proline content under stress conditions. Moreover, overexpression plants were hypersensitive to ABA at both germination and post-germination stages and accumulated more endogenous ABA under drought stress conditions. Further studies demonstrated that overexpression of OsMYB48-1 could regulate the expression of some ABA biosynthesis genes (OsNCED4, OsNCED5), early signaling genes (OsPP2C68, OSRK1) and late responsive genes (RAB21, OsLEA3, RAB16C and RAB16D) under drought stress conditions. Collectively, these results suggested that OsMYB48-1 functions as a novel MYB-related TF which plays a positive role in drought and salinity tolerance by regulating stress-induced ABA synthesis.
The Comparability of English, French and Dutch Scores on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F): An Assessment of Differential Item Functioning in Patients with Systemic Sclerosis

Objective The Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F) is commonly used to assess fatigue in rheumatic diseases, and has shown to discriminate better across levels of the fatigue spectrum than other commonly used measures. The aim of this study was to assess the cross-language measurement equivalence of the English, French, and Dutch versions of the FACIT-F in systemic sclerosis (SSc) patients. Methods The FACIT-F was completed by 871 English-speaking Canadian, 238 French-speaking Canadian and 230 Dutch SSc patients. Confirmatory factor analysis was used to assess the factor structure in the three samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess differential item functioning (DIF), comparing English versus French and versus Dutch patient responses separately. Results A unidimensional factor model showed good fit in all samples. Comparing French versus English patients, statistically significant, but small-magnitude DIF was found for 3 of 13 items. French patients had 0.04 of a standard deviation (SD) lower latent fatigue scores than English patients and there was an increase of only 0.03 SD after accounting for DIF. For the Dutch versus English comparison, 4 items showed small, but statistically significant, DIF. Dutch patients had 0.20 SD lower latent fatigue scores than English patients. After correcting for DIF, there was a reduction of 0.16 SD in this difference. Conclusions There was statistically significant DIF in several items, but the overall effect on fatigue scores was minimal. English, French and Dutch versions of the FACIT-F can be reasonably treated as having equivalent scoring metrics.
Recommendations on the use of ruxolitinib for the treatment of myelofibrosis

ABSTRACT Objectives: Myelofibrosis (MF) is a severe disease, with decreased life expectancy and heavy symptom burden. Ruxolitinib is the only approved pharmacotherapy for the treatment of MF patients. In Belgium, ruxolitinib is only reimbursed for MF patients with splenomegaly for whom the disease is categorized as intermediate-2 or high risk. The improvement of symptoms without spleen volume reduction is not considered sufficient to continue treatment. The aim of this manuscript is to provide guidance for the safe and effective administration of ruxolitinib, considering the particularities of the Belgian reimbursement criteria. Methods: Our recommendations are based on a consensus reached during two meetings, where available data and observations derived from clinical experience were discussed. Results and discussion: We recommend changing the current Belgian reimbursement conditions to include the evaluation of disease-related symptoms along with splenomegaly to decide whether ruxolitinib treatment should be continued or not. Indeed, the decrease in disease-related symptoms seems to be an equally important parameter as the decrease in splenic volume in the evaluation of the response to ruxolitinib. We also advocate for the treatment with ruxolitinib of MF patients in lower-risk categories with severe disease-related symptoms, as this drug could greatly improve their quality of life. Optimization of the ruxolitinib dose is recommended to avoid an unnecessary decrease in platelet count or hemoglobin that may jeopardize treatment continuation. Conclusion: With the aim to optimize the treatment of MF patients, the Belgian regulation for ruxolitinib should be revised in terms of reimbursement criteria, dose titration, stopping rules, and patient follow-up.
Evolving criteria for the diagnosis of antibody-mediated rejection in renal allografts

Purpose of review To review changes in the Banff schema for antibody-mediated renal allograft rejection over the past decade, including key revisions agreed upon during and immediately subsequent to the 2017 Banff Conference on Allograft Pathology. Recent findings The original Banff schema for diagnosis of acute and chronic active antibody-mediated rejection (ABMR) in renal allografts was formulated at the 2001 and 2007 Banff Conferences, and required histologic (primarily microvascular inflammation and transplant glomerulopathy), immunohistologic (C4d in peritubular capillaries), and serologic [circulating donor-specific antibodies (DSA)] evidence for a definitive diagnosis of ABMR. This schema was updated at the 2013 Banff Conference, recognizing C4d-negative ABMR, intimal arteritis as a potential manifestation of ABMR, and revising definitions and thresholds for glomerulitis and transplant glomerulopathy to improve interobserver agreement and correlation with clinical, molecular, and serologic data. Compared with the 2007 criteria, Banff 2013 improved the sensitivity of the classification for diagnosing ABMR and the correlation of ABMR diagnosis with graft outcomes. At the 2017 Banff Conference, new modifications to the classification were discussed and have subsequently been agreed upon, accepting C4d and thoroughly validated molecular classifiers as surrogate markers for DSA. Summary From a consensus reached at the 2017 Banff Conference, updated criteria for diagnosis of active and chronic active ABMR have been developed that recognize C4d and molecular classifiers as surrogate markers for DSA. In addition, specific recommendations for the use of molecular diagnostics in the diagnosis of ABMR were developed.
Estimating Daytime Ecosystem Respiration to Improve Estimates of Gross Primary Production of a Temperate Forest

Leaf respiration is an important component of carbon exchange in terrestrial ecosystems, and estimates of leaf respiration directly affect the accuracy of ecosystem carbon budgets. Leaf respiration is inhibited by light; therefore, gross primary production (GPP) will be overestimated if the reduction in leaf respiration by light is ignored. However, few studies have quantified GPP overestimation with respect to the degree of light inhibition in forest ecosystems. To determine the effect of light inhibition of leaf respiration on GPP estimation, we assessed the variation in leaf respiration of seedlings of the dominant tree species in an old mixed temperate forest with different photosynthetically active radiation levels using the Laisk method. Canopy respiration was estimated by combining the effect of light inhibition on leaf respiration of these species with within-canopy radiation. Leaf respiration decreased exponentially with an increase in light intensity. Canopy respiration and GPP were overestimated by approximately 20.4% and 4.6%, respectively, when leaf respiration reduction in light was ignored compared with the values obtained when light inhibition of leaf respiration was considered. This study indicates that accurate estimates of daytime ecosystem respiration are needed for the accurate evaluation of carbon budgets in temperate forests. In addition, this study provides a valuable approach to accurately estimate GPP by considering leaf respiration reduction in light in other ecosystems.
Immediate and Persistent Transcriptional Correlates of Long-Term Sensitization Training at Different CNS Loci in Aplysia californica

Repeated noxious stimulation produces long-term sensitization of defensive withdrawal reflexes in Aplysia californica, a form of long-term memory that requires changes in both transcription and translation. Previous work has identified 10 transcripts which are rapidly up-regulated after long-term sensitization training in the pleural ganglia. Here we use quantitative PCR to begin examining how these transcriptional changes are expressed in different CNS loci related to defensive withdrawal reflexes at 1 and 24 hours after long-term sensitization training. Specifically, we sample from a) the sensory wedge of the pleural ganglia, which exclusively contains the VC nociceptor cell bodies that help mediate input to defensive withdrawal circuits, b) the remaining pleural ganglia, which contain withdrawal interneurons, and c) the pedal ganglia, which contain many motor neurons. Results from the VC cluster show different temporal patterns of regulation: 1) rapid but transient up-regulation of Aplysia homologs of C/EBP, C/EBPγ, and CREB1, 2) delayed but sustained up-regulation of BiP, Tolloid/BMP-1, and sensorin, 3) rapid and sustained up-regulation of Egr, GlyT2, VPS36, and an uncharacterized protein (LOC101862095), and 4) an unexpected lack of regulation of Aplysia homologs of calmodulin (CaM) and reductase-related protein (RRP). Changes in the remaining pleural ganglia mirror those found in the VC cluster at 1 hour but with an attenuated level of regulation. Because these samples had almost no expression of the VC-specific transcript sensorin, our data suggests that sensitization training likely induces transcriptional changes in either defensive withdrawal interneurons or neurons unrelated to defensive withdrawal. In the pedal ganglia, we observed only a rapid but transient increase in Egr expression, indicating that long-term sensitization training is likely to induce transcriptional changes in motor neurons but raising the possibility of different transcriptional endpoints in this cell type.
Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede*

Centipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes mutilans. Nine hundred twenty-three and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified ∼10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in centipede, similar to snakes.
Pharmaceutics, Drug Delivery and Pharmaceutical Technology In Vivo Performance of Fenofibrate Formulated With Ordered Mesoporous Silica Versus 2-Marketed Formulations: A Comparative Bioavailability Study in Beagle Dogs

The present study aims to evaluate the in vitro and in vivo performance of ordered mesoporous silica (OMS) as a carrier for the poorly water-soluble compound fenofibrate. Fenofibrate was loaded into OMS via incipient wetness impregnation to obtain a 29% drug load and formulated into capsules. Two capsule dosage forms (containing 33.5 and 16.75 mg fenofibrate, respectively) were compared with the commercially available formsdLipanthyl ® (fenofibrate microcrystals) and Tricor ® (fenofibrate nanocrystals). In vitro dissolution tests showed that the amount of fenofibrate released from Lipanthyl ® and Tricor ® was approximately 30%, whereas approximately 66% and 60% of the drug was released from OMS capsules containing 33.5 and 16.75 mg of fenofibrate, respectively. Storage of OMS capsules loaded with 33.5 mg of fenofibrate at 25 � C/60% relative humidity (RH) or 40 � C/75% RH did not alter the release kinetics, nor the physical state of the compound, pointing the stability of the present formulation. The in vivo study in dogs confirmed satisfying level of safety and tolerability of fenofibrateeOMS formulation (eq. 33.5 mg) with the potential to improve the absorption of fenofibrate. Though some variability in the data, this formulation is promising to be further investigated in a clinical trial setting. © 2016 American Pharmacists Association