Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormal total ejection isovolume index as early noninvasive marker of chronic rejection in heart transplantation *

Abnormally high myocardial performance index (MPI) is a Doppler‐derived marker of combined systolic and diastolic left ventricular (LV) dysfunction. To identify early stage allograft dysfunction by MPI, we studied 154 long‐term heart transplantation (HT) recipients (131 male, aged 51 ± 13 years at HT, mean follow up 8.4 ± 3.5 years), with normal left ventricular ejection fraction (LVEF) and free from acute rejection (AR), and 25 normals (13 male, aged 39 ± 16 years). Rejection score (RS) on endomyocardial biopsy was calculated in the first year. MPI was prolonged (0.45 ± 0.18 vs. 0.28 ± 0.10, P = 0.0001) in patients and directly related with mean time from HT (P = 0.001), higher cumulative dosages of cyclosporine at 3 months (P = 0.01), 6 months (P = 0.03), 1 year (P = 0.02), 3 years (P = 0.04) and with cumulative dosage of methylprednisolone at 1 year (P = 0.002). The index was inversely related with mean age at HT (P = 0.002) and tended to be directly related with RS at 1 year (P = 0.05). Thus, MPI is abnormal in long‐term HT recipients with normal LVEF. Its direct relation with time from HT as well as immunosuppressive load suggests an early stage of graft dysfunction because of chronic rejection. Extended prospective studies are warranted to clarify its potential role as a negative prognostic marker in HT.
CDKN2A homozygous deletion is associated with muscle invasion in FGFR3‐mutated urothelial bladder carcinoma

The gene cyclin‐dependent kinase inhibitor 2A (CDKN2A) is frequently inactivated by deletion in bladder carcinoma. However, its role in bladder tumourigenesis remains unclear. We investigated the role of CDKN2A deletion in urothelial carcinogenesis, as a function of FGFR3 mutation status, a marker for one of the two pathways of bladder tumour progression, the Ta pathway. We studied 288 bladder carcinomas: 177 non‐muscle‐invasive (123 Ta, 54 T1) and 111 muscle‐invasive (T2–4) tumours. CDKN2A copy number was determined by multiplex ligation‐dependent probe amplification, and FGFR3 mutations by SNaPshot analysis. FGFR3 mutation was detected in 124 tumours (43.1%) and CDKN2A homozygous deletion in 56 tumours (19.4%). CDKN2A homozygous deletion was significantly more frequent in FGFR3‐mutated tumours than in wild‐type FGFR3 tumours (p = 0.0015). This event was associated with muscle‐invasive tumours within the FGFR3‐mutated subgroup (p < 0.0001) but not in wild‐type FGFR3 tumours. Similar findings were obtained for an independent series of 101 bladder carcinomas. The impact of CDKN2A deletions on recurrence‐free and progression‐free survival was then analysed in 89 patients with non‐muscle‐invasive FGFR3‐mutated tumours. Kaplan–Meier survival analysis showed that CDKN2A losses (hemizygous and homozygous) were associated with progression (p = 0.0002), but not with recurrence, in these tumours. Multivariate Cox regression analysis identified CDKN2A loss as a predictor of progression independent of stage and grade. These findings highlight the crucial role of CDKN2A loss in the progression of non‐muscle‐invasive FGFR3‐mutated bladder carcinomas and provide a potentially useful clinical marker for adapting the treatment of such tumours, which account for about 50% of cases at initial clinical presentation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Seeking causes: Classifying and evaluating congenital heart defects in etiologic studies.

BACKGROUND Classification and analysis of congenital heart defects (CHD) in etiologic studies is particularly challenging because of diversity of cardiac phenotypes and underlying developmental mechanisms. We describe an approach to classification for risk assessment of CHD based on developmental and epidemiologic considerations, and apply it to data from the National Birth Defect Prevention Study (NBDPS). METHODS The classification system incorporated the three dimensions of cardiac phenotype, cardiac complexity, and extracardiac anomalies. The system was designed to facilitate the assessment of simple isolated defects and common associations. A team with cardiologic expertise applied the system to a large sample from the NBDPS. RESULTS Of the 4,703 cases of CHDs in the NBDPS with birth years 1997 through 2002, 63.6% were simple, isolated cases. Specific associations of CHDs represented the majority of the remainder. The mapping strategy generated relatively large samples for most cardiac phenotypes and provided enough detail to isolate important subgroups of CHDs that may differ by etiology or mechanism. CONCLUSIONS Classification of CHDs that considers cardiac and extracardiac phenotypes is practically feasible, and yields manageable groups of well-characterized phenotypes. Although best suited for large studies, this approach to classification and analysis can be a flexible and powerful tool in many types of etiologic studies of heart defects.
Insulin-Like Growth Factors in the Pathogenesis of Neurological Diseases in Children

Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy–hypsarrhythmia–optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum disorders (ASD) and subacute sclerosing encephalopathy (SSPE) have been carried out? What are IGF-based therapeutic strategies? What are the therapeutic approaches? We conclude that there are now great hopes for the therapeutic use of IGF-1 for some neurological disorders (particularly ASD).
Sex differences in time to task failure and blood flow for an intermittent isometric fatiguing contraction

The purpose of this study was to compare the time to task failure, postcontraction hyperemia, and vascular conductance of young men and women for a submaximal intermittent fatiguing contraction performed with the handgrip muscles. Twenty men and 20 women (mean ± SD: 22 ± 4 years) performed an isometric contraction at 50% of maximal voluntary contraction (MVC) (6‐s contraction, 4‐s rest) until task failure. Forearm venous occlusion plethysmography was used to estimate the peak blood flow (after 10‐min occlusion) and blood flow at rest after 6‐s submaximal contractions of varying intensities, and during an intermittent fatiguing contraction at 1‐min intervals and task failure. The time to task failure was longer for the women compared with the men (408 ± 205 s vs. 297 ± 57 s, P < 0.05). Postcontraction hyperemia and vascular conductance were greater for men than for women after nonfatiguing 6‐s submaximal contractions performed at 20%, 40%, 50%, 60%, and 80% of MVC force (P < 0.05). In contrast, hyperemia and vascular conductance were similar for both genders when measured at 50 s into the fatiguing contraction, at each minute thereafter, and at task failure. Regression analysis indicated that the rate of electromyographic activity and perceived exertion were the significant predictors of the time to task failure. The longer time to task failure for women compared with men for an intermittent fatiguing contraction with handgrip muscles was not explained by postcontraction hyperemia or vascular conductance with fatigue. © 2008 Wiley Periodicals, Inc. Muscle Nerve 39: 42–53, 2009
Morphology of the tongue dorsal surface of gilthead seabream (Sparus aurata)

The gilthead seabream is a food fish, one of the most frequently used in aquaculture. In the species of commercial interest, feeding in captivity is very important and this process is strictly related to the morphological characteristics of the oral cavity. The aim of this study is, using the standard procedures for light and scanning electron microscopy, to analyze the morphology of the tongue dorsal surface to show if relationships are present between the tongue morphology and the nutritional habits and choices of this farmed species. The main characteristic of the gilthead seabream oral cavity floor is the presence of an apical pouch, with, probably, a protective role mainly for the apical, free part of the tongue. Three zones, like in other teleosts, an apex, a body and a root, can be clearly distinguished. In the pouch foliate‐like papillae were observed, while the whole tongue is characterized by the presence of two types of papillae, respectively with a fungiform and cylindroid aspect, both randomly distributed throughout the whole dorsal surface of the tongue. Scattered and numerous taste buds, with the typical pear‐onion shape, together with small and numerous taste pores are also present, distributed throughout the tongue surface. Our results demonstrate that in the gilthead seabream important mechanic and sensory roles are carried out by specific anatomical structures. Our anatomical data could give, together with further biochemical and physiological data, an important support with the aim of improving the nutrition of aquaculture species. Microsc. Res. Tech. © 2012 Wiley Periodicals, Inc.
Reactive oxygen species in leaf abscission signaling

Reactive oxygen species (ROS) are produced in response to many environmental stresses, such as UV, chilling, salt, and pathogen attack. These stresses also accompany leaf abscission in some plants, however, the relationship between these stresses and abscission is poorly understood. In our recent report, we developed an in vitro abscission system that reproduces stress-induced pepper leaf abscission in planta. Using this system, we demonstrated that continuous production of hydrogen peroxide (H2O2) is involved in leaf abscission signaling. Continuous H2O2 production is required to induce expression of the cell wall-degrading enzyme, cellulase, and functions downstream of ethylene in abscission signaling. Furthermore, enhanced production of H2O2 occurs at the execution phase of abscission, suggesting that H2O2 also plays a role in the cell-wall degradation process. These data suggest that H2O2 has several roles in leaf abscission signaling. Here, we propose a model for these roles. Addendum to: Sakamoto M, Munemura I, Tomita R, Kobayashi K. Involvement of hydrogen peroxide in leaf abscission signaling revealed by analysis with an in vitro abscission system in Capsicum plants. Plant J 2008; doi: 10.1111/j.1365-313X.2008. 03577.x
Prevention of ultraviolet‐induced skin pigmentation

Background/purpose: Exposure to ultraviolet (UV) radiation increases skin pigmentation and usually results in an even darkening of the skin. However, it may also occasionally lead to the development of hyperpigmented lesions due to a local overproduction of pigment. Skin pigmentation is induced both by UVB and UVA rays.
Identification and quantification of coronary atherosclerotic plaques: a comparison of 64-MDCT and intravascular ultrasound.

OBJECTIVE The purpose of this study was to compare the accuracy of 64-MDCT with that of intravascular ultrasound (IVUS) for the identification and quantitative analysis of coronary atherosclerotic plaques. MATERIALS AND METHODS Twenty-six patients (17 men, nine women; mean age, 56 years) with suspected coronary atherosclerotic disease were studied using contrast-enhanced 64-MDCT and IVUS. The coronary arteries were divided into 10-mm segments and vascular cross-sectional area (CSA), luminal CSA, and plaque burden were measured in each segment. Plaque analysis software was used to automatically detect both plaques and vessel walls on CT images. Two investigators who were blinded to IVUS results independently determined the presence, classification, and quantitative measurement of atherosclerotic plaques on the CT images, which were then compared with the IVUS images. RESULTS Of 40 coronary arteries, 247 of 263 segments were imaged and analyzed by both contrast-enhanced 64-MDCT and IVUS. Sixteen segments were ruled out because of poor CT image quality. Compared with IVUS, 64-MDCT enabled correct detection in 86 of 89 (96.6%) segments containing noncalcified plaques, 25 of 27 (92.6%) segments containing calcified plaques, and 118 of 131 (90.1%) segments without atherosclerotic plaques. Sensitivity, specificity, positive predictive value, and negative predictive value for the detection of plaques by 64-MDCT were 97.4%, 90.1%, 89.7%, and 97.5%, respectively. Plaque analysis software using predetermined Hounsfield unit ranges for different components of plaque was able to distinguish between fibrous, fibrous-soft, and calcified plaques to a significant degree, but was less able to distinguish between soft and fibrous, and between soft and fibrous-soft plaque. Cohen's kappa coefficient for the sole detection of atherosclerotic segments by observers was 0.91. The correlation coefficients to determine vascular CSA, luminal CSA, and plaque burden were r = 0.85, 0.82, and 0.77, respectively (p < 0.01). CONCLUSION Compared with IVUS, contrast-enhanced 64-MDCT has a good ability to identify and quantify coronary atherosclerotic plaques. However, the reliable differentiation of the composition of noncalcified plaques is still limited.
ETHYLENE-INSENSITIVE 3 Is a Senescence-Associated Gene That Accelerates Age-Dependent Leaf Senescence byDirectly Repressing miR 164 Transcription in Arabidopsis

Numerous endogenous and environmental signals regulate the intricate and highly orchestrated process of plant senescence. Ethylene is a well-known inducer of senescence, including fruit ripening and flower and leaf senescence. However, the underlying molecular mechanism of ethylene-induced leaf senescence remains to be elucidated. Here, we examine ETHYLENE-INSENSITIVE3 (EIN3), a key transcription factor in ethylene signaling, and find that EIN3 is a functional senescence-associated gene. Constitutive overexpression or temporary activation of EIN3 is sufficient to accelerate leaf senescence symptoms. Conversely, loss of EIN3 and EIN3-Like1 (its close homolog) function leads to a delay in agedependent and ethylene-, jasmonic acid-, or dark-induced leaf senescence. We further found that EIN3 acts downstream of ORESARA2 (ORE2)/ORE3/EIN2 to repress miR164 transcription and upregulate the transcript levels of ORE1/NAC2, a target gene of miR164. EIN3 directly binds to the promoters of microRNA164 (miR1640), and this binding activity progressively increases during leaf ageing. Genetic analysis revealed that overexpression of miR164 or knockout of ORE1/NAC2 represses EIN3-induced early-senescence phenotypes. Collectively, our study defines a continuation of the signaling pathway involving EIN2-EIN3-miR164-NAC2 in regulating leaf senescence and provides a mechanistic insight into how ethylene promotes the progression of leaf senescence in Arabidopsis thaliana.
Industrial Haptic Robot Guidance System for assembly processes

Human haptic sense is an important aspect for numerous assembly processes, especially in manual assembly, where the worker uses this sense to identify the occurring contact forces and tries to reduce them. Such an act minimizes the risk of unintended collisions or deformation of parts and thus guarantees a successful completion of the assembly process. Although the assembly of small/medium lots is normally carried out manually by a worker, the help of robots is mandatory in some cases, where the ability of the human being is hindered, such as the assembly of heavy parts. Some industrial robotic systems are available in the market, in which the robot is guided by a human operator to perform some tasks. However, those systems lack the haptic feedback. This work aims at the design and evaluation of an industrial Haptic Robot Guidance System (HRGS). The main role of the HRGS in assembly is to combine both human haptic sense and industrial robot capability. In this paper some research issues and approaches for the design of HRGS are introduced. Some preliminary experimental results are also included.
Outbreak of Carbapenem-Resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-β-Lactamase, in a Tertiary Care Center in Cali, Colombia

ABSTRACT The prevalence of imipenem resistance among Pseudomonas aeruginosa isolates at a 195-bed tertiary care medical center in Cali, Colombia, rose from 2% in 1996 to 28% in 1997 and to over 40% in 2003. Many isolates showed high-level multiresistance, and phenotypic characterization suggested the spread of a predominant strain with minor variants. Sixty-six resistant isolates collected between February 1999 and July 2003 from hospitalized patients (n = 54) and environmental samples (n = 12) were subjected to a fuller analysis. Genetic fingerprints were compared by pulsed-field gel electrophoresis (PFGE) of SpeI-digested genomic DNA, and blaIMP and blaVIM genes were sought by PCR. PFGE and serotyping indicated that 52 of the 66 isolates belonged to a single strain, with 82% similarity; the PFGE pattern for this organism was designated pattern A. Two further pairs of isolates represented single strains; the remaining nine isolates were unique, and in the case of one isolate, no satisfactory PFGE profile could be obtained. The pattern A isolates were mostly of serotype O12 and were highly resistant to imipenem (MICs, 32 to >256 μg/ml), with this resistance decreased eightfold or more in the presence of EDTA. They yielded amplicons with blaVIM-specific primers, and sequencing of DNA from a representative isolate revealed blaVIM-8, a novel allele with three polymorphisms compared with the sequence of blaVIM-2. Two of these nucleotide changes were silent, but the third determined a Thr139Ala substitution. Only 4 of 13 resistant isolates (2 clinical isolates and 2 environmental isolates) assigned to other PFGE types carried blaVIM alleles, whereas the others were less multiresistant and mostly had lower levels of imipenem resistance (MICs, ≤32 μg/ml) which was not significantly reduced by EDTA. No blaIMP alleles were detected. During 2003, when the environmental study was undertaken, serotype O12 isolates with blaVIM were recovered from sinks and stethoscopes in the most-affected units, although not from the hands of staff; the problem declined once these reservoirs were disinfected and hygienic precautions were reinforced.
Theory of the high-frequency chiral optical response of a p(x) + ip(y) superconductor.

The optical Hall conductivity and the polar Kerr angle are calculated as functions of temperature for a two-dimensional chiral p(x) + ip(y) superconductor, where the time-reversal symmetry is spontaneously broken. The theoretical estimate for the polar Kerr angle agrees by the order of magnitude with the recent experimental measurement in Sr2RuO4 by Xia et al. [Phys. Rev. Lett. 97, 167002 (2006)10.1103/PhysRevLett.97. 167002]. The theory predicts that the Kerr angle is proportional to the square of the superconducting energy gap and is inversely proportional to the cube of frequency, which can be verified experimentally.
Down‐regulation of CREB‐binding protein expression inhibits thrombin‐induced proliferation of endothelial cells: possible relevance to PDGF‐B

Thrombin acts as a potent mitogenic factor for ECs (endothelial cells) by the release of several growth factors, including PDGF‐B (platelet‐derived growth factor‐B). CBP (CREB‐binding protein), which functions as a transcriptional coactivator, links the changes in the extracellular stimuli with alterations in gene expression. Therefore, we hypothesized that CBP could mediate thrombin‐induced proliferation of ECs via PDGF‐B‐dependent way. Short hairpin RNA was used to down‐regulate the expression of CBP in ECs. CBP and PDGF‐B levels were analysed by real‐time RT‐PCR and Western blot. To evaluate ECs proliferation, cell cycle and DNA synthesis were analysed by flow cytometry and BrdU (bromodeoxyuridine) incorporation assay, respectively. PDGF‐B was involved in the mitogenic effect of thrombin on ECs. Down‐regulation of CBP attenuated ECs proliferation and inhibited cell cycle progression induced by thrombin. Silencing CBP expression also suppressed thrombin‐induced PDGF‐B expression in ECs. Mitogenic activity of thrombin was impaired by silencing CBP expression in ECs. This inhibitory effect was, in part, related to the inability to up‐regulate PDGF‐B expression in ECs. CBP could be regarded as a potential therapeutic target for vascular injury.
Evaluation of the Effects of a Psychosocial Intervention on Mood, Coping, and Quality Of Life in Cancer Patients

It was hypothesized that participation in a psychosocial intervention incorporating meditation, social support, positive thinking, and a low-fat, vegetarian diet would have beneficial effects on mood, coping, and quality of life (QOL) in cancer patients. This article describes the sociodemographic, medical, and psychological characteristics of participants in a psychosocial intervention designed for cancer patients. It also describes program impact in terms of Profile of Mood States, Mini-Mental Adjustment to Cancer, and Functional Assessment of Chronic Illness Therapy. Compliance with program recommendations for 3 months and effects on adjustment were also explored. Improvements in all measures were found at program completion, with spiritual well-being particularly linked to improvement in QOL. The results suggest that the program has significant beneficial effects on adjustment but that these may not be fully maintained at follow-up, possibly because of difficulty in incorporating program recommendations into everyday life, increasing disease severity, and lack of accountability.
Genetic covariance between gamma-glutamyl transpeptidase and fatty liver risk factors: role of beta2-adrenergic receptor genetic variation in twins.

BACKGROUND & AIMS Plasma levels of gamma-glutamyl transpeptidase (GGT) are associated with risk factors for nonalcoholic fatty liver disease (NAFLD), such as dyslipidemia, insulin resistance (IR), and hypertension. Limited data exist on whether there is genetic covariance between plasma levels of GGT and NAFLD risk factors. Variants of beta2-adrenergic receptor gene (ADRB2) have been associated with dyslipidemia, IR, and hypertension, but its effect on GGT secretion is not known. We estimated the heritability of GGT using a twin-study design and examined the genetic covariance between GGT levels, IR, hypertension, levels of low-density lipoproteins and triglycerides, and ADRB2 variants. METHODS We studied phenotypes of 362 twins; the heritabilities of increased GGT activity and genetic covariance with NAFLD risk factors were estimated by variance-component methodology. ADRB2 genotype associations with plasma GGT activity were examined using generalized estimating equations to account for intra-twinship correlations. RESULTS GGT activity was heritable at 49% +/- 8% of the twin cohort and had significant covariance with IR; insulin, triglyceride, and uric acid levels; and diastolic blood pressure. In generalized estimating equation models, the most common haplotype of ADRB2 was significantly associated with plasma GGT activity. Five single nucleotide polymorphisms in ADRB2 were associated with levels of GGT; ADRB2 haplotypes displayed pleiotropic effects on GGT and triglyceride levels. CONCLUSIONS In a twin study, GGT shared genetic codetermination with traits of metabolic syndrome. The ADRB2 gene had pleiotropic effects on plasma levels of GGT and triglycerides, indicating linked pathways (eg, adrenergic) between genetic susceptibility to NAFLD and metabolic syndrome.