Miracle-dz/UniFAR-FTUs huggingface dataset:
Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival.

OBJECTIVE The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM. METHODS A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival. RESULTS A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02-1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95-0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31-0.83]; p = 0.0067) to be significantly associated with survival. CONCLUSION This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.
Echocardiography by a neonatologist

Editor,—As to who should perform echocardiography,1 I report the experience of a neonatal intensive care unit in Townsville, 1500 km from the cardiac centre in Brisbane, Australia. Echocardiography is performed by a neonatologist using a Toshiba 140 with colour Doppler. There is ready access to the machine and it is used liberally to monitor sick babies, …
Model-based iterative reconstruction versus adaptive statistical iterative reconstruction and filtered back projection in liver 64-MDCT: focal lesion detection, lesion conspicuity, and image noise.

OBJECTIVE The purpose of this study is to compare three CT image reconstruction algorithms for liver lesion detection and appearance, subjective lesion conspicuity, and measured noise. MATERIALS AND METHODS Thirty-six patients with known liver lesions were scanned with a routine clinical three-phase CT protocol using a weight-based noise index of 30 or 36. Image data from each phase were reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR). Randomized images were presented to two independent blinded reviewers to detect and categorize the appearance of lesions and to score lesion conspicuity. Lesion size, lesion density (in Hounsfield units), adjacent liver density (in Hounsfield units), and image noise were measured. Two different unblinded truth readers established the number, appearance, and location of lesions. RESULTS Fifty-one focal lesions were detected by truth readers. For blinded reviewers compared with truth readers, there was no difference for lesion detection among the reconstruction algorithms. Lesion appearance was statistically the same among the three reconstructions. Although one reviewer scored lesions as being more conspicuous with MBIR, the other scored them the same. There was significantly less background noise in air with MBIR (mean [± SD], 2.1 ± 1.4 HU) than with ASIR (8.9 ± 1.9 HU; p < 0.001) or FBP (10.6 ± 2.6 HU; p < 0.001). Mean lesion contrast-to-noise ratio was statistically significantly higher for MBIR (34.4 ± 29.1) than for ASIR (6.5 ± 4.9; p < 0.001) or FBP (6.3 ± 6.0; p < 0.001). CONCLUSION In routine-dose clinical CT of the liver, MBIR resulted in comparable lesion detection, lesion characterization, and subjective lesion conspicuity, but significantly lower background noise and higher contrast-to-noise ratio compared with ASIR or FBP. This finding suggests that further investigation of the use of MBIR to enable dose reduction in liver CT is warranted.
Effects of selective thalamic and prelimbic cortex lesions on two types of visual discrimination and reversal learning

The effects of excitotoxic lesions of the mediodorsal nucleus of the thalamus, the anterior thalamic nuclei and of the prelimbic cortex were examined on two tests of discrimination and reversal learning. In experiment 1A (visual discrimination and reversal), rats were required to discriminate two stimuli, and respond to the stimulus associated with reward (the S+ stimulus). There was no effect of lesion on acquisition of this task. However, when stimulus–reward contingencies were reversed, animals with lesions of the mediodorsal nucleus of the thalamus made significantly more errors than control animals or animals of other lesion groups. In experiment 1B (conditional discrimination), animals were required to learn a rule of the type ‘If stimulus A then go left, if stimulus B then go right’. No main effect of lesion on acquisition was observed in this experiment. To test the generality of the reversal effect obtained in experiment 1A, a second cohort of animals with the same lesions was tested on acquisition of the visuospatial conditional task immediately postsurgery, followed by the reversal of the conditional rule (experiment 2). As in experiment 1B, no main effect of lesion group was observed during acquisition of the task. However, lesions of the mediodorsal nucleus of the thalamus resulted in a mild impairment according to number of sessions required to attain criterion performance of the task when the response rule was reversed. The results of the present study provide evidence for a role for the mediodorsal nucleus of the thalamus in new learning, particularly when stimulus–reward contingencies are reversed. Furthermore, they show that the functions of this thalamic nucleus can be dissociated from those of the anterior thalamus and the prelimbic cortex.
Highly Active Antiretroviral Therapy Attenuates Re-Endothelialization and Alters Neointima Formation in the Rat Carotid Artery After Balloon Injury

Summary:Highly active antiretroviral therapy (HAART) has led to a sustained decline of HIV-associated morbidity and mortality. HAART exhibits significant side effects, however, such as hyperlipidemia and hyperglycemia, which possibly contribute to accelerated atherosclerosis in HAART-treated patients. In addition, direct effects of HAART on vascular cells have been described, which may promote atherosclerotic lesion formation. The effects of HAART on balloon-induced neointima formation have not been studied previously. The rat carotid artery balloon model was used to evaluate the effects of HAART (lopinavir, ritonavir, lamivudine, and zidovudine) on neointima formation and endothelial recovery. Furthermore, the effects of concomitant administration of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor rosuvastatin were investigated. HAART-treated animals displayed an increase in lesion size (neointima/media ratio: 1.14 ± 0.32 vs. 1.31 ± 0.20 in control vs. HAART; P < 0.05) and an impaired regenerative capacity of the endothelium, as indicated by reduction in endothelial regrowth from an adjacent undilated vessel segment 14 days after injury (re-endothelialization area: 8.29 ± 1.45 mm2 vs. 5.09 ± 0.53 mm2 in control vs. HAART; P < 0.05). When rosuvastatin was given in addition to HAART, these effects were not observed. In conclusion, HAART inhibited endothelial cell-mediated healing and promoted neointima formation after angioplasty in rats. These deleterious effects were attenuated by cotreatment with rosuvastatin, however. Our studies suggest that currently used drug regimens against HIV infection may lead to an increased risk for restenosis after percutaneous vascular interventions. Moreover, the findings indicate that the additional treatment with statins might counteract these adverse effects by HAART.
Knowledge creation and play: A phenomenological study within a multi-professional and multi-organizational community

Purpose The purpose of this paper is to present a framework for empirically studying knowledge creation (KC) with phenomenological approach and propose that understanding interaction as play conceptualized by Hans-Georg Gadamer allows examining KC starting from the idea of a human being interacting in the events of co-creation. The presented framework is used to examine KC in a community of librarians and teachers collaborating to promote children’s joy of reading. Design/methodology/approach An ethnographic approach is applied to investigate knowledge-creating interaction in a working community. The triangulated data consist of ethnographic observations and video recordings of the community’s gatherings, its members’ interviews and produced documents. Findings The phenomenological conceptions of temporality of a human being and play are suitable for understanding being in the knowledge-creating interaction, as they give means to understand the meaningfulness of the past experiences, but promote an open attitude toward the future possibilities in a way which promotes KC. Studying interactive events allows understanding how KC can be examined as a collective accomplishment. The playful mode of being in the event was seen as a way to use the limited time available for interaction effectively. Research limitations/implications The empirical study was conducted in one community, and further research is needed to test the developed approach in other contexts. Practical implications The results may be utilized to develop organizational circumstances, which promote KC by acknowledging the meaningfulness of interaction. Originality/value The study presents a novel way to conceptualize and examine KC as an experience and an event with phenomenological approach.
Current advances in treatment of gastroparesis

Introduction: Gastroparesis is a syndrome defined by delayed gastric emptying in the absence of mechanical obstruction. Gastroparesis has significant symptomatology and negative impacts on the patient’s quality of life. Areas covered: This article reviews current treatment options for gastroparesis, recent advances in treatment and future directions that treatment may head. Current options are broadly divided into prokinetics and symptom modulators. Within each group, current modalities as well as recent advances are discussed according to agent mechanism of action. Lastly, findings regarding the cellular pathophysiology involved in gastroparesis will be briefly reviewed along with their implications for future treatments. Expert opinion: The numerous motor functions and neural inputs that control gastric motility are complex and not fully understood. Our lack of understanding of its pathophysiology has led to treatment options which are empirical, palliative and often ineffective. Newly intensified interest in the cellular pathophysiology behind gastroparesis provides promise for a new era of treatments. Identification of common cellular changes in gastroparesis has provided targets for treatment that may allow us to one day better treat the symptoms of gastroparesis related to its underlying pathophysiology. This is the future of gastroparesis therapy.
Aneuploid embryonic stem cells exhibit impaired differentiation and increased neoplastic potential

Aneuploidy leads to severe developmental defects in mammals and is also a hallmark of cancer. However, whether aneuploidy is a driving cause or a consequence of tumor formation remains controversial. Paradoxically, existing studies based on aneuploid yeast and mouse fibroblasts have shown that aneuploidy is usually detrimental to cellular fitness. Here, we examined the effects of aneuploidy on mouse embryonic stem (ES) cells by generating a series of cell lines that each carries an extra copy of single chromosomes, including trisomy 6, 8, 11, 12, or 15. Most of these aneuploid cell lines had rapid proliferation rates and enhanced colony formation efficiencies. They were less dependent on growth factors for self‐renewal and showed a reduced capacity to differentiate in vitro. Moreover, trisomic stem cells formed teratomas more efficiently, from which undifferentiated cells can be recovered. Further investigations demonstrated that co‐culture of wild‐type and aneuploid ES cells or supplementation with extracellular BMP4 rescues the differentiation defects of aneuploid ES cells.
FliG Subunit Arrangement in the Flagellar Rotor Probed by Targeted Cross-Linking

ABSTRACT FliG is a component of the switch complex on the rotor of the bacterial flagellum. Each flagellar motor contains about 25 FliG molecules. The protein of Escherichia coli has 331 amino acid residues and comprises at least two discrete domains. A C-terminal domain of about 100 residues functions in rotation and includes charged residues that interact with the stator protein MotA. Other parts of the FliG protein are essential for flagellar assembly and interact with the MS ring protein FliF and the switch complex protein FliM. The crystal structure of the middle and C-terminal parts of FliG shows two globular domains joined by an α-helix and a short extended segment that contains two well-conserved glycine residues. Here, we describe targeted cross-linking studies of FliG that reveal features of its organization in the flagellum. Cys residues were introduced at various positions, singly or in pairs, and cross-linking by a maleimide or disulfide-inducing oxidant was examined. FliG molecules with pairs of Cys residues at certain positions in the middle domain formed disulfide-linked dimers and larger multimers with a high yield, showing that the middle domains of adjacent subunits are in fairly close proximity and putting constraints on the relative orientation of the domains. Certain proteins with single Cys replacements in the C-terminal domain formed dimers with moderate yields but not larger multimers. On the basis of the cross-linking results and the data available from mutational and electron microscopic studies, we propose a model for the organization of FliG subunits in the flagellum.
Organization of nuclear architecture during adipocyte differentiation

ABSTRACT Obesity is a serious health problem worldwide since it is a major risk factor for chronic diseases such as type II diabetes. Obesity is the result of hyperplasia (associated with increased adipogenesis) and hypertrophy (associated with decreased adipogenesis) of the adipose tissue. Therefore, understanding the molecular mechanisms underlying the process of adipocyte differentiation is relevant to delineate new therapeutic strategies for treatment of obesity. As in all differentiation processes, temporal patterns of transcription are exquisitely controlled, allowing the acquisition and maintenance of the adipocyte phenotype. The genome is spatially organized; therefore decoding local features of the chromatin language alone does not suffice to understand how cell type-specific gene expression patterns are generated. Elucidating how nuclear architecture is built during the process of adipogenesis is thus an indispensable step to gain insight in how gene expression is regulated to achieve the adipocyte phenotype. Here we will summarize the recent advances in our understanding of the organization of nuclear architecture as progenitor cells differentiate in adipocytes, and the questions that still remained to be answered.
Chylothorax in chronic lymphocytic leukemia patient

Chronic lymphocytic leukemia (CLL) is rarely complicated by chylothorax: we present a 93‐year‐old woman with CLL who developed recurrent pleural effusions that were ultimately found to be chylous in nature. Despite eight repeated thoracenteses, she continued to experience re‐accumulation of fluid, and therefore, video‐assisted thoracotomy with mass ligation of the thoracic duct region plus pleurodesis was performed to resolve the chylothorax. Despite her age and underlying disease, she did well during follow‐up. The etiology and management of chylothorax are also reviewed. Am. J. Hematol. 70:237–240, 2002. © 2002 Wiley‐Liss, Inc.
Age‐related changes in topological organization of structural brain networks in healthy individuals

The aim of this study was to examine structural brain networks using regional gray matter volume, as well as to investigate changes in small‐world and modular organization with normal aging. We constructed structural brain networks composed of 90 regions in young, middle, and old age groups. We randomly selected 350 healthy subjects for each group from a Japanese magnetic resonance image database. Structural brain networks in three age groups showed economical small‐world properties, providing high global and local efficiency for parallel information processing at low connection cost. The small‐world efficiency and node betweenness varied significantly and revealed a U‐ or inverted U‐curve model tendency among three age groups. Results also demonstrated that structural brain networks exhibited a modular organization in which the connections between regions are much denser within modules than between them. The modular organization of structural brain networks was similar between the young and middle age groups, but quite different from the old group. In particular, the old group showed a notable decrease in the connector ratio and the intermodule connections. Combining the results of small‐world efficiency, node betweenness and modular organization, we concluded that the brain network changed slightly, developing into a more distributed organization from young to middle age. The organization eventually altered greatly, shifting to a more localized organization in old age. Our findings provided quantitative insights into topological principles of structural brain networks and changes related to normal aging. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
The effects of idiotype on the ability of IgG1 antiphosphorylcholine antibodies to protect mice from fatal infection with Streptococcus pneumoniae

Anti‐phosphorylcholine (PC) antibodies of the mouse are found in three different idiotype families: T15, M603 and M511. These subgroups exhibit different specificities for PC analogs and utilize light chains of different VL subgroups. In this study we have found that IgG1 antibodies of the T15 idiotype are much more protective against pneumococcal infection than IgG1 antibodies of the M511 or M603 idiotypes. This finding provides additional evidence that the T15 VH and VL genes may have evolved to protect mice from infection with PC‐bearing pathogens.
Exhaled breath analysis by electronic nose in respiratory diseases

Breath analysis via electronic nose is a technique oriented around volatile organic compound (VOC) profiling in exhaled breath for diagnostic and prognostic purposes. This approach, when supported by methodologies for VOC identification, has been often referred to as metabolomics or breathomics. Although breath analysis may have a substantial impact on clinical practice, as it may allow early diagnosis and large-scale screening strategies while being noninvasive and inexpensive, some technical and methodological limitations must be solved, together with crucial interpretative issues. By integrating a review of the currently available literature with more speculative arguments about the potential interpretation and application of VOC analysis, the authors aim to provide an overview of the main relevant aspects of this promising field of research.
Magnet arrays for use in a 3-D MEMS mirror array for optical switching

In this paper, we present magnet array development as part of 3D electromagnetic MEMS mirror arrays for use in optical switching applications. An electromagnetic mirror array uses an external array of magnets positioned under the array of mirrors to provide a strong magnetic field at the mirrors. Each mirror contains multiple coils which interact with the external magnetic fields to produce two orthogonal torques.
Simultaneous determination of mercury methylation and demethylation capacities of various sulfate‐reducing bacteria using species‐specific isotopic tracers

The use of species‐specific isotopic tracers for inorganic and methyl mercury has allowed the simultaneous determination of the methylation and demethylation potentials of pure culture of isolated sulfate‐reducing (SR) bacterial strains using low Hg species concentration levels (7 µg/L 199Hg(II), 1 µg/L Me201Hg). A major advantage of the method reported here is that it can be used to follow simultaneously both the degradation of the species added but also the formation of their degradation products and thus the determination during the same incubation of the specific methylation/demethylation yields and rate constants. Methylation/demethylation capacities and extents have been found to differ between the tested strains and the tested conditions. The methylating/demethylating capacities of bacteria appear to be strain specific. All the methylating strains were found to demethylate methylmercury (MeHg). The active mechanism responsible for Hg methylation appears directly dependent on the bacterial activity but is not dependent on the metabolism used by the tested bacteria (sulfate reduction, fermentation, or nitrate respiration). The results provide confirmation that SR strains contribute to MeHg demethylation under anoxic conditions, leading to Hg(II) as the end product, consistent with the oxidative degradation pathway. Kinetic experiments have allowed specific transformation rate constants to be addressed for the two reversible processes and the reactivity of each isotopic tracer to be compared. The differential reactivity highlighted the different steps involved in the two apparent processes (i.e., uptake plus internal transformation of mercury species). Methylation appears as the slowest process, mainly controlled by the assimilation of Hg(II), whereas demethylation is faster and not dependent on the MeHg concentration. Environ. Toxicol. Chem. 2011;30:337–344. © 2010 SETAC