Miracle-dz/UniFAR-FTUs huggingface dataset:
Axenfeld‐Rieger syndrome: Further clinical and array delineation of four unrelated patients with a 4q25 microdeletion

Axenfeld‐Rieger syndrome (ARS) is an autosomal dominant disorder with variable expressivity. It is characterized by dysgenesis of the anterior segment of the eye together with dental, cardiac, and umbilical anomalies. There is a high incidence of secondary high tension glaucoma. It is a genetically heterogeneous condition due to deletion or mutations of FOXC1 (6p25) or PITX2 (4q25). We report on four unrelated patients with overlapping microdeletions encompassing PITX2 at 4q25. We compare the genotypes and phenotypes of these newly described ARS patients and discuss the involvement of contiguous genes. Patients 1, 2, and 3 had mild learning difficulties, not typically seen in patients with ARS. We implicate the adjacent neuronally expressed genes; NEUROG2, UGT8, NDST3, and PRSS12 as potentially causal. Our findings support the use of microarray analysis in ARS patients for full prognostic information in infants presenting with ARS‐like phenotypes. © 2014 Wiley Periodicals, Inc.
The time reversal invariant fractional Josephson effect

One of the most basic consequences of topological superconductivity is the fractional Josephson effect, which arises due to the coherent tunneling of single electrons between two superconductors, leading to an ac Josephson effect with half the usual Josephson frequency. In this paper we will review the theoretical and experimental foundations of topological superconductivity and the fractional Josephson effect. We will then describe recent work in which we have clarified the role of time reversal symmetry. We find that time reversal symmetric Josephson junctions are classified by two distinct Z2 topological invariants. One of these characterizes a junction mediated by the edge states of a quantum spin Hall insulator. In that case, we showed that electron interactions stabilize a ‘Z4 fractional Josephson effect’ with one quarter the usual Josephson frequency. For strong interactions this Josephson effect is associated with the tunneling of charge e / 2 ? > quasiparticles. For weak tunneling, this theory describes a fourfold ground state degeneracy that is similar to that of coupled ‘fractional’ Majorana modes, but is protected by time reversal symmetry.
Structural Diversity in the 5′-Untranslated Region of Cytokine-stimulated Human Inducible Nitric Oxide Synthase mRNA (*)

Inducible nitric oxide synthase, the critical enzyme responsible for the enhanced synthesis of nitric oxide in inflammatory states, is widely expressed in mammalian cells. To evaluate potential regulatory roles of the 5′-untranslated region (UTR) in the human inducible nitric oxide synthase gene, the transcription initiation sites and structure of the 5′-UTR of human inducible nitric oxide synthase were examined. Freshly isolated human alveolar macrophages, bronchial epithelial cells, and several types of cultured cells were evaluated following stimulation with cytokines (i.e. interferon-, interleukin-1β, tumor necrosis factor-α, and interleukin-6). The mRNA was analyzed by reverse transcription-polymerase chain reaction, Northern analysis, and 5′-rapid amplification of cDNA ends. Despite the presence of a TATA box in the promoter region, multiple transcription initiation sites were observed, some extending several hundred base pairs upstream from the main TATA-directed initiation site. Alternative splicing in the 5′-UTR of human inducible nitric oxide synthase mRNA resulted in further diversity. The TATA-independent inducible nitric oxide synthase mRNA transcripts were up-regulated by cytokines. The long and complex 5′-UTRs contain eight partially overlapping open reading frames upstream of the putative inducible nitric oxide synthase ATG, which may have an important role in translational regulation of human inducible nitric oxide synthase mRNA.
Effectiveness of 3D T2-Weighted FLAIR FSE Sequences with Fat Suppression for Detection of Brain MR Imaging Signal Changes in Children

BACKGROUND AND PURPOSE: T2-weighted FLAIR can be combined with 3D-FSE sequences with isotropic voxels, yielding higher signal-to-noise ratio than 2D-FLAIR. Our aim was to explore whether a T2-weighted FLAIR–volume isotropic turbo spin-echo acquisition sequence (FLAIR-VISTA) with fat suppression shows areas of abnormal brain T2 hyperintensities with better conspicuity in children than a single 2D-FLAIR sequence. MATERIALS AND METHODS: One week after a joint training session with 20 3T MR imaging examinations (8 under sedation), 3 radiologists independently evaluated the presence and conspicuity of abnormal areas of T2 hyperintensities of the brain in FLAIR-VISTA with fat suppression (sagittal source and axial and coronal reformatted images) and in axial 2D-FLAIR without fat suppression in a test set of 100 3T MR imaging examinations (34 under sedation) of patients 2–18 years of age performed for several clinical indications. Their agreement was measured with weighted κ statistics. RESULTS: Agreement was “substantial” (mean, 0.61 for 3 observers; range, 0.49–0.69 for observer pairs) for the presence of abnormal T2 hyperintensities and “fair” (mean, 0.29; range, 0.23–0.38) for the comparative evaluation of lesion conspicuity. In 21 of 23 examinations in which the 3 radiologists agreed on the presence of abnormal T2 hyperintensities, FLAIR-VISTA with fat suppression images were judged to show hyperintensities with better conspicuity than 2D-FLAIR. In 2 cases, conspicuity was equal, and in no case was conspicuity better in 2D-FLAIR. CONCLUSIONS: FLAIR-VISTA with fat suppression can replace the 2D-FLAIR sequence in brain MR imaging protocols for children.
Influenza A-Associated Meningoencephalitis

Complications of influenza such as meningitis or encephalitis are rarely seen in the United States. There have been multiple case reports of patients in other parts of the world involving children with severe illness, neurologic sequelae, or death. Many of these reported cases were during influenza epidemics. We report on 2 children who presented as isolated cases in the United States with a less severe course and better outcome than previously reported.
Zoo U: A Stealth Approach to Social Skills Assessment in Schools

This paper describes the design and evaluation of Zoo U, a novel computer game to assess children's social skills development. Zoo U is an innovative product that combines theory-driven content and customized game mechanics. The game-like play creates the opportunity for stealth assessment, in which dynamic evidence of social skills is collected in real time and players' choices during gameplay provide the needed data. To ensure the development of an engaging and valid game, we utilized an iterative datadriven validation process in which the game was created, tested, revised based on student performance and feedback, and retested until game play was statistically matched to independent ratings of social skills. We first investigated whether the data collected through extensive logging of student actions provided information that could be used to improve the assessment. We found that detailed game logs of socially relevant player behavior combined with external measures of player social skills provided an efficient vector to incrementally improve the accuracy of the embedded assessments. Next, we investigated whether the game performance correlated with teachers' assessments of students' social skills competencies. An evaluation of the final game showed (a) significant correlations between in-game social skills assessments and independently obtained standard psychological assessments of the same students and (b) high levels of engagement and likeability for students. These findings support the use of the interactive and engaging computer game format for the stealth assessment of children's social skills. The created innovative design methodologies should prove useful in the design and improvement of computer games in education.
Clomipramine versus sertraline in the treatment of obsessive compulsive disorder

Objective: The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Method: Outpatients met the DSM-IV criteria for OCD for 1 year or longer and scores of . 20 on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and . 4 on the Clinical Global Impression Severity Scale (CGI-S) were included in the study. Patients who had significant concomitant physical disease, suicidal tendency, a history of seizure or organic brain disorder, substance abuse within the previous sixth months, DSM-IV axis I diagnoses other than OCD and who had had medication for 1 month were not included in the study.Patients were randomized to receive 8- week of single-blind treatment with either fixed dose of sertraline (n=20) 50 mg/day or clomipramine (n=22) initially 50 mgĞday and 150 mg/day after 1 week. No additional medication was given to patients. Clinical evaluations were conducted before the treatment and on two-week schedule throughout the 8-week trial using the Y-BOCS and theCGI-S. Results: Four of clomipramine (18.2%) and 2 of sertraline (10.0%) patients dropped out because of adverse events or lack of effectiveness. Thirty six patients completed the trial (sertraline n=18; clomipramine n=18). The mean baseline Y-BOCS and CGI-S scores were 24.95 and 4.75 respectively for sertraline and 23.54 and 4.85 for clomipramine (p>0.05). A significant reduction in OCD symptoms from baseline to the end of 8 th week of the trial was found in both sertraline and clomipramine treated groups (p0.05). The number of patients withdrawn because of adverse events was substantially greater for clomipramine (22.2%) than sertraline (11.1%). The incidence of side effects was significantly higher in clomipraminetreated patients versus sertraline-treated patients. The most frequent adverse events with sertraline were headache (38.8%), nausea (33.3%), irritability (11.1%) and tremor (11.1%), while clomipramine was most commonly associated with dry mouth (50%), weight gain (50%), constipation (27.7%), yawning (27.7%), sedation (22.2%) and dizziness (11.1%). Conclusions: At fixed doses, both clomipramine and sertraline showed a similar therapeutic efficacy in the treatment of OCD. Clomipramine produced more side effects and dropout rate. The results indicate that sertraline is as effective as clomipramine in the treatment of OCD and is better tolerated.
A narrower gap of grazing intensity. Reply to Fetzel et al., 2017. Seasonality constrains to livestock grazing intensity

Fil: Irisarri, Jorge Gonzalo Nicolas. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Parque Centenario. Instituto de Investigaciones Fisiologicas y Ecologicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomia; Argentina
Aging, rhythms of physical performance, and adjustment to changes in the sleep-activity cycle.

OBJECTIVES: Shiftwork causes disturbances of the normal sleep-wake cycle and circadian rhythm. There is concern that aging workers have more problems than younger counterparts when the human body clock is disrupted. This review considers issues relating to aging, the circadian body clock, and adjustment to altered sleep-wake schedules. METHODS: Reports on effects of aging on the human body clock were reviewed. Research concerned with adjustment to circadian phase shifts (as occurs in night work) was considered. RESULTS: With aging there is an increased tendency towards morningness which is linked with difficulties in sleeping. The peak time and amplitude of normal circadian rhythms are altered. Tolerance of shiftwork can be linked with social factors as well as adaptation of the body clock. CONCLUSIONS: People habituated to night work seem to have developed mechanisms which allow them to cope with disruptions to lifestyle and the endogenous body clock. Elderly people are more suited to phase advances, as occur in morning workshifts, than to phase delays such as nocturnal work.
Retinal Laser Burn-Induced Neuropathy Leads to Substance P-Dependent Loss of Ocular Immune Privilege

Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time. In an effort to explain the inflammation in the nonburned eye, we postulated that neuronal signals initiated inflammation in the contralateral eye. In this study, we test the role of substance P, a neuroinflamatory peptide, in RLB-induced loss of ACAID. Histological examination of the retina with and without RLB revealed an increase of the substance P-inducible neurokinin 1 receptor (NK1-R) in the retina of first, the burned eye, and then the contralateral eye. Specific antagonists for NK1-R, given locally with Ag within 24 h, but not 3, 5, or 7 d post-RLB treatment, prevented the bilateral loss of ACAID. Substance P knockout (KO) mice retained their ability to develop ACAID post-RLB. These data support the postulate that substance P transmits early inflammatory signals from the RLB eye to the contralateral eye to induce changes to ocular immune privilege and has a central role in the bilateral loss of ACAID. The possibility is raised that blocking of the substance P pathway with NK1-R antagonists postocular trauma may prevent unwanted and perhaps extended consequences of trauma-induced inflammation in the eye.
The effects of aortic coarctation on cerebral hemodynamics and its importance in the etiopathogenesis of intracranial aneurysms.

OBJECTIVES Hemodynamic changes in the cerebral circulation in presence of coarctation of aorta (CoA) and their significance in the increased intracranial aneurysms (IAs) formation in these patients remain unclear. In the present study, we measured the flow-rate waveforms in the cerebral arteries of a patient with CoA, followed by an analysis of different hemodynamic indices in a coexisting IA. MATERIALS AND METHODS Phase-contrast Magnetic Resonance (pc-MR) volumetric flow-rate (VFR) measurements were performed in cerebral arteries of a 51 years old woman with coexisting CoA, and five healthy volunteers. Numerical predictions of a number of relevant hemodynamic indices were performed in an IA located in sub-clinoid part of left internal carotid artery (ICA) of the patient. Computations were performed using Ansys(®)-CFX(™) solver using the VFR values measured in the patient as boundary conditions (BCs). A second analysis was performed using the average VFR values measured in healthy volunteers. The VFR waveforms measured in the patient and healthy volunteers were compared followed by a comparison of the hemodynamic indices obtained using both approaches. The results are discussed in the background of relevant literature. RESULTS Mean flow-rates were increased by 27.1% to 54.9% (2.66-5.44 ml/sec) in the cerebral circulation of patients with CoA as compared to healthy volunteers (1.2-3.95 ml/sec). Velocities were increased inside the IA by 35-45%. An exponential rise of 650% was observed in the area affected by high wall shear stress (WSS>15Pa) when flow-rates specific to CoA were used as compared to population average flow-rates. Absolute values of space and time averaged WSS were increased by 65%. Whereas values of maximum pressure on the IA wall were increased by 15% the area of elevated pressure was actually decreased by 50%, reflecting a more focalized jet impingement within the IA of the CoA patient. CONCLUSIONS IAs can develop in patients with CoA several years after the surgical repair. Cerebral flow-rates in CoA patients are significantly higher as compared to average flow-rates in healthy population. The increased supra-physiological WSS (>15Pa), OSI (>0.2) and focalized pressure may play an important role in the etiopathogenesis of IAs in patients with CoA.
Seasonal fluctuations of nematode populations in breeding ewes and lambs.

The seasonal changes in nematode populations of a flock of sheep in the Montreal area were determined using serial fecal egg counts, fecal culture of larvae and necropsy worm counts. It was found that Ostertagia spp. ,Nematodirus spp. , Trichostrongylus agei, Trichostrongylus spp. and Chabertia ovina over-wintered on pasture and could initiate patent infections the following spring. The development of populations of H. contortus was typical of that seen with most of the other species and was characterized by the following series of events. In early winter when the study was started with stabled pregnant ewes, most of the populations were immature and the egg counts were low and remained so throughout the entire winter. However, in the spring, following lambing, large numbers of adult worms were seen with a consequent decrease in immatures and a sudden increase in egg counts. When the ewes and lambs were pastured together, the egg counts in ewes dropped consequent to "self-cure", the "spring-rise" providing the major source of overwhelming infections for lambs with deaths by the end of July. As the season progressed larvae taken in by both ewes and lambs did not mature, and by early fall, most of the worm population consisted of immature forms. It appeared that H. contortus could not have more than two generations in ewes or lambs in a single grazing season.
Suture absorption in rabbit cornea and sclera: enzyme histochemical and morphologic observations.

Plain and chromic size 6-0 ophthalmic catgut sutures were implanted in rabbit cornea, sclera, and ocular muscle. Enzyme histochemical procedures (acid and alkaline phosphatase, adenosine triphosphatase, aminopeptidase, and succinic dehydrogenase) were applied to cryostat sections of the sites at weekly postimplantation intervals between 3 and 60 days. Tissue reaction and suture absorption rates were also noted. When compared to the findings previously observed in gluteal muscle implants, the corneal sites showed predominant alkaline phosphatase activity and more rapid absorption, whereas the scleral sites provided variable results. The findings in ocular muscle were similar to those in gluteal muscle implants. A wide morphological variation was observed in the cells invading the body of corneal sutures during absorption, which was completed by 21 days with the plain suture and by 60 days icith the chromic sample.
High-affinity salicylic acid-binding protein 2 is required for plant innate immunity and has salicylic acid-stimulated lipase activity

Salicylic acid (SA) is a critical hormone for signaling innate immunity in plants. Here we present the purification and characterization of SA-binding protein 2 (SABP2), a tobacco protein that is present in low abundance and specifically binds SA with high affinity. Sequence analysis predicted that SABP2 is a lipase belonging to the α/β fold hydrolase super family. Confirming this prediction, recombinant SABP2 exhibited lipase activity against several synthetic substrates. Moreover, this lipase activity was stimulated by SA binding and may generate a lipid-derived signal. Silencing of SABP2 expression suppressed local resistance to tobacco mosaic virus, induction of pathogenesis-related 1 (PR-1) gene expression by SA, and development of systemic acquired resistance. Together, these results suggest that SABP2 is an SA receptor that is required for the plant immune response. We further propose that SABP2 belongs to a large class of ligand-stimulated hydrolases involved in stress hormone-mediated signal transduction.
Bacteriologic and clinical efficacy of amoxicillin/clavulanate vs. azithromycin in acute otitis media

Objectives. To compare the bacteriologic and clinical efficacy of amoxicillin/clavulanate and azithromycin in patients with acute otitis media (AOM), particularly the ability to eradicate the predominant AOM pathogens from middle ear fluid as assessed by mandatory second tympanocentesis. Methods. In this single blind study 238 infants and children with AOM were randomized to receive amoxicillin/clavulanate (45/6.4 mg/kg/day in two divided doses for 10 days) or azithromycin (10 mg/kg on Day 1, then 5 mg/kg daily on Days 2 through 5). Tympanocentesis was performed before the first dose and repeated on Day 4, 5 or 6. Clinical response was assessed at end of therapy between Days 12 and 14 and at follow‐up between Days 22 and 28. Results. Amoxicillin/clavulanate was significantly more likely to eradicate all bacterial pathogens [83% (54 of 65) vs. 49% (35 of 71), P = 0.001] and Haemophilus influenzae [87% (26 of 30) vs. 39% (13 of 33), P = 0.0001] from middle ear fluid than was azithromycin. Amoxicillin/clavulanate was also more likely to eradicate Streptococcus pneumoniae, but the difference was not statistically significant [90% (18 of 20) vs. 68% (3 of 19), P = 0.095]. On Days 12 to 14, signs and symptoms were more likely to resolve completely or improve in all culture‐positive patients [86% (60 of 70) vs. 70% (51 of 73), P = 0.023] and in those with H. influenzae infections [91% (30 of 33) vs. 65% (22 of 34), P = 0.010] who received amoxicillin/clavulanate compared with those who received azithromycin. Otherwise there were no significant differences between groups in clinical outcomes on Days 12 to 14 or at follow‐up. Conclusions. Our findings indicate that amoxicillin/clavulanate has superior bacteriologic and clinical efficacy compared with azithromycin in children with AOM.
Analysis of TP53 Mutation Status in Human Cancer Cell Lines: A Reassessment

Tumor‐derived cell lines play an important role in the investigation of tumor biology and genetics. Across a wide array of studies, they have been tools of choice for the discovery of important genes involved in cancer and for the analysis of the cellular pathways that are impaired by diverse oncogenic events. They are also invaluable for screening novel anticancer drugs. The TP53 protein is a major component of multiple pathways that regulate cellular response to various types of stress. Therefore, TP53 status affects the phenotype of tumor cell lines profoundly and must be carefully ascertained for any experimental project. In the present review, we use the 2014 release of the UMD TP53 database to show that TP53 status is still controversial for numerous cell lines, including some widely used lines from the NCI‐60 panel. Our analysis clearly confirms that, despite numerous warnings, the misidentification of cell lines is still present as a silent and neglected issue, and that extreme care must be taken when determining the status of p53, because errors may lead to disastrous experimental interpretations. A novel compendium gathering the TP53 status of 2,500 cell lines has been made available (http://p53.fr). A stand‐alone application can be used to browse the database and extract pertinent information on cell lines and associated TP53 mutations. It will be updated regularly to minimize any scientific issues associated with the use of misidentified cell lines (http://p53.fr).
Reconfigurable radiation pattern antenna based on active frequency selective surfaces

In this paper, a prototype of AFSS screen based on the simple dipole strips has been proposed for a reconfigurable radiation pattern antenna. The results achieved in the measurements confirm the expected objectives for the proposed structure. However, it has been observed that the parasitic elements created by the active elements are indeed the main problem in attainting the desired properties. Because of this, the position of bandgap significantly changes which it leads to an in complete transparent screen in one state. However, measurement results demonstrate that using this idea it is possible to achieve a reconfigurable radiation pattern. Study on this subject is undergoing to improve the performance of the antenna.