julilili42/papers huggingface dataset:
Drug-Eluting Balloon Therapy for Femoropopliteal Occlusive Disease
2015-08-06

Purpose: To assess the association of patient, lesion, and procedure variables, including calcification, with late lumen loss (LLL) after use of drug-eluting balloon (DEB) therapy in patients with femoropopliteal arterial disease. Methods: In this retrospective study, 91 patients (mean age 72.0±8.62 years; 50 men) were analyzed at 6 months after DEB treatment. Lesions were located in the superficial femoral artery (SFA, n=68) and popliteal artery (n=23). Lesion calcification was graded by a core laboratory using 2 published scoring indices: the peripheral artery calcification scoring system and a grading system based on circumference (arc) and length of calcium. Results: The median LLL after 6 months was 0.2 mm (interquartile range −0.5, 1.14) overall and varied significantly across lesions with differing severity of calcification (p=0.042). However, LLL did not differ based on calcium location (intimal, medial, or mixed) or calcium length (p=0.351 and p=0.258, respectively). Additional predictors of LLL after DEB treatment included diabetes (p=0.034), coronary artery disease (p=0.024), and prior intervention (p=0.013). Interestingly, the severity of residual stenosis after the intervention did not have any impact on the LLL during follow-up (Spearman r = −0.238). Conclusion: Severity of lesion calcification is associated with LLL after treatment with DEB. One possible approach to overcome this limitation might be plaque modification or removal prior to DEB usage. Nevertheless, clinical data that support this hypothesis are currently lacking.
Early subtropical forest growth is driven by community mean trait values and functional diversity rather than the abiotic environment
2015-08-06

Abstract While functional diversity ( FD ) has been shown to be positively related to a number of ecosystem functions including biomass production, it may have a much less pronounced effect than that of environmental factors or species‐specific properties. Leaf and wood traits can be considered particularly relevant to tree growth, as they reflect a trade‐off between resources invested into growth and persistence. Our study focussed on the degree to which early forest growth was driven by FD , the environment (11 variables characterizing abiotic habitat conditions), and community‐weighted mean ( CWM ) values of species traits in the context of a large‐scale tree diversity experiment ( BEF ‐China). Growth rates of trees with respect to crown diameter were aggregated across 231 plots (hosting between one and 23 tree species) and related to environmental variables, FD , and CWM , the latter two of which were based on 41 plant functional traits. The effects of each of the three predictor groups were analyzed separately by mixed model optimization and jointly by variance partitioning. Numerous single traits predicted plot‐level tree growth, both in the models based on CWM s and FD , but none of the environmental variables was able to predict tree growth. In the best models, environment and FD explained only 4 and 31% of variation in crown growth rates, respectively, while CWM trait values explained 42%. In total, the best models accounted for 51% of crown growth. The marginal role of the selected environmental variables was unexpected, given the high topographic heterogeneity and large size of the experiment, as was the significant impact of FD , demonstrating that positive diversity effects already occur during the early stages in tree plantations.
Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin
2015-08-06

ABSTRACT Vimentin (Vim) and glial fibrillary acidic protein (GFAP) are important components of the intermediate filament (IF) (or nanofilament) system of astroglial cells. We conducted full‐field electroretinogram (ERG) recordings and found that whereas photoreceptor responses (a‐wave) were normal in uninjured GFAP –/– Vim –/– mice, b‐wave amplitudes were increased. Moreover, we found that Kir (inward rectifier K + ) channel protein expression was reduced in the retinas of GFAP –/– Vim –/– mice and that Kir‐mediated current amplitudes were lower in Müller glial cells isolated from these mice. Studies have shown that the IF system, in addition, is involved in the retinal response to injury and that attenuated Müller cell reactivity and reduced photoreceptor cell loss are observed in IF‐deficient mice after experimental retinal detachment. We investigated whether the lack of IF proteins would affect cell survival in a retinal ischemia‐reperfusion model. We found that although cell loss was induced in both genotypes, the number of surviving cells in the inner retina was lower in IF‐deficient mice. Our findings thus show that the inability to produce GFAP and Vim affects normal retinal physiology and that the effect of IF deficiency on retinal cell survival differs, depending on the underlying pathologic condition.—Wunderlich, K. A., Tanimoto, N., Grosche, A., Zrenner, E., Pekny, M., Reichenbach, A., Seeliger, M. W., Pannicke, T., Perez, M.‐T. Retinal functional alterations in mice lacking intermediate filament proteins glial fibrillary acidic protein and vimentin. FASEB J. 29, 4815–4828 (2015). www.fasebj.org
A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance
2015-08-06

Patients carrying very rare loss‐of‐function mutations in interleukin‐1 receptor–associated kinase 4 ( IRAK4 ), a critical signaling mediator in Toll‐like receptor signaling, are severely immunodeficient, highlighting the paramount role of IRAK kinases in innate immunity. We discovered a comparatively frequent coding variant of the enigmatic human IRAK2 , L392V (rs3844283), which is found homozygously in ∼15% of Caucasians, to be associated with a reduced ability to induce interferon‐alpha in primary human plasmacytoid dendritic cells in response to hepatitis C virus (HCV). Cytokine production in response to purified Toll‐like receptor agonists was also impaired. Additionally, rs3844283 was epidemiologically associated with a chronic course of HCV infection in two independent HCV cohorts and emerged as an independent predictor of chronic HCV disease. Mechanistically, IRAK2 L392V showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor–associated factor 6, a vital step in signal transduction. Conclusion : Our study highlights IRAK2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity. (H epatology 2015;62:1375–1387)
Quantification of β-Amyloidosis and rCBF with Dedicated PET, 7 T MR Imaging, and High-Resolution Microscopic MR Imaging at 16.4 T in APP23 Mice
2015-08-06

Our dual-modality imaging approach using 11C-PIB PET/7 T MR imaging and 16.4 T microscopic MR imaging allowed amyloid-load quantification with high sensitivity and high resolution, the identification of substructures within single amyloid plaques, and the quantification of rCBF.
Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade
2015-08-07

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep−wake disorders ( SWD s) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWD s may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep−wake function ( SWF ) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWD s that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre‐graduate and postgraduate teaching, creating academic multidisciplinary sleep−wake centres and simplifying diagnostic approaches of SWD s coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.
Hierarchical fragmentation and collapse signatures in a high-mass starless region
2015-08-07

Aims: Understanding the fragmentation and collapse properties of the dense\\ngas during the onset of high-mass star formation. Methods: We observed the\\nmassive (~800M_sun) starless gas clump IRDC18310-4 with the Plateau de Bure\\nInterferometer (PdBI) at sub-arcsecond resolution in the 1.07mm continuum\\nandN2H+(3-2) line emission. Results: Zooming from a single-dish low-resolution\\nmap to previous 3mm PdBI data, and now the new 1.07mm continuum observations,\\nthe sub-structures hierarchically fragment on the increasingly smaller spatial\\nscales. While the fragment separations may still be roughly consistent with\\npure thermal Jeans fragmentation, the derived core masses are almost two orders\\nof magnitude larger than the typical Jeans mass at the given densities and\\ntemperatures. However, the data can be reconciled with models using\\nnon-homogeneous initial density structures, turbulence and/or magnetic fields.\\nWhile most sub-cores remain (far-)infrared dark even at 70mum, we identify weak\\n70mum emission toward one core with a comparably low luminosity of ~16L_sun,\\nre-enforcing the general youth of the region. The spectral line data always\\nexhibit multiple spectral components toward each core with comparably small\\nline widths for the individual components (in the 0.3 to 1.0km/s regime). Based\\non single-dish C18O(2-1) data we estimate a low virial-to-gas-mass ratio\\n&lt;=0.25. We discuss that the likely origin of these spectral properties may be\\nthe global collapse of the original gas clump that results in multiple spectral\\ncomponents along each line of sight. Even within this dynamic picture the\\nindividual collapsing gas cores appear to have very low levels of internal\\nturbulence.\\n
Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia
2015-08-07

Objectives. Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. Methods. Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. Results. No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10–8) in our GWA study, but 10 SNPs reached P-values less than 10–6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. Conclusions. Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.
Fruit flies, bile acids, and Parkinson disease
2015-08-08

Parkinson disease (PD) has been strongly associated with systemic defects in mitochondrial function. The best characterized of these is probably reduced activity of complex I of the electron transport chain, which was first reported more than 25 years ago,1 after the discovery of the pro-parkinsonian toxin, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), and its mechanism of action: inhibition of complex I.2 Proof-of-concept that a systemic impairment of complex I can reproduce the selective nigrostriatal degeneration and Lewy pathology of PD came from the rotenone model of PD in rats in 2000.3 Shortly thereafter, it became clear that certain autosomal recessive forms of PD are caused by mutations in genes that affect mitochondrial function or quality control, such as parkin and PINK1 . Moreover, both parkin and PINK1 mutations are associated with a loss of complex I activity.4,5
Imaging in Minimally Invasive Mitral Valve Repair
2015-08-08

Minimally invasive mitral valve (MV) repair and replacement techniques have evolved as increasingly used alternatives to open heart surgery especially in patients unsuitable for surgery or at high perioperative risk. The vast majority of these techniques are still under development, and only a limited number of devices are approved for clinical use; however, they do show promising results in terms of minimizing complications and improving clinical outcome. The complex anatomy of the MV and the annulus complicates not only the development of devices for minimally invasive MV repair or replacement but also complicates preprocedural planning, which is mandatory for minimization of postprocedural complications. Although echocardiography still plays a crucial clinical role, cross-sectional imaging modalities such as coronary computed tomography (CCT) and cardiac magnetic resonance imaging (CMR) are increasingly gaining importance for preprocedural planning. Specifically, CCT seems to be more practicable for preinterventional planning and device sizing, whereas CMR has been shown useful in detecting increased risk for adverse clinical outcomes through delayed gadolinium enhancement and the monitoring of cardiac morphology and function in the framework of follow-up examinations. This article describes recent techniques currently available or under development for minimally invasive repair or replacement of the MV and reviews the current state of CCT and CMR imaging for preinterventional and postinterventional diagnostic workup.
Botulinum toxin B increases intrinsic muscle activity in organotypic spinal cord–skeletal muscle co-cultures
2015-08-08

In organotypic spinal cord-skeletal muscle co-cultures, motoneurons are driven by locomotor commands and induce contractions in surrounding muscle fibres. Using these co-cultures, it has been shown that effects of organophosphorus compounds on neuromuscular synapses can be determined in vitro. In the present study we aimed to extend this in vitro tool for pharmacologic testing of botulinum toxin B. This neurotoxin is widely used for the treatment of dystonia. Besides its effects on the neuromuscular junction, botulinum toxins may also act at centrally located synapses. Incubation with botulinum toxin B (Neurobloc(®)) induced a significant increase in muscular activity after 24, 48 and 72h. Application of the NMDA- and AMPA-receptor antagonists AP5 (20μM) and CNQX (15μM) induced a similar augmentation of muscle activity after 48 and 72h, respectively. Administration of the glycine- and GABA(A)-receptor antagonists strychnine (1μM) and bicuculline (100μM) did not alter intrinsic muscle activity. In contrast, application of a non-depolarizing muscle relaxant rocuronium bromide reduced the muscle activity in a dose-dependent manner. Our findings suggest that glutamatergic synapses in the spinal cord are more sensitive to botulinum toxin B than synaptic contacts between spinal motoneurons and muscle fibres.
Systems biology definition of the core proteome of metabolism and expression is consistent with high-throughput data
2015-08-10

Significance Defining a core functional proteome supporting the living process has importance for both developing fundamental understanding of cell functions and for synthetic biology applications. Comparative genomics has been the primary approach to achieve such a definition. Here, we use genome-scale models to define a core proteome that computationally supports basic cellular function. This core proteome for metabolism and protein expression, defined through systems biology methods, is validated and characterized by using multiple disparate data types.
Antioxidants may Attenuate Plasma Erythropoietin Decline after Hyperbaric Oxygen Diving
2015-08-10

According to previous studies, plasma erythropoietin (EPO) may decrease after hyperbaric oxygen exposure due to oxidative stress. It is hypothesized that the decrease of EPO can be attenuated by oxygen free radical scavengers.The aim of the present study was to evaluate whether EPO plasma levels can be influenced by oral application of vitamin C and E before repeated hyperbaric oxygen exposure during diving. 16 healthy male police task force divers performed 3 morning dives on oxygen within a regular diving schedule on 3 consecutive days. They were randomized into either the placebo group or the vitamin group, receiving 1 g ascorbic acid and 600 IU D-α-tocopherol orally 60 min before the dive. Blood samples for EPO measurement were taken on days 1, 2, and 3 at T1, T3 and T5 60 min before and at T2, T4 and T6 60 min after each dive, respectively. A moderate decrease of EPO was observed beginning at T3 until T6 in the placebo group. The EPO concentrations in the vitamin group did not show relevant variations compared to baseline. Radical scavenging vitamins C and D may counteract hyperbaric oxygen related mechanisms reducing EPO production in hyperbaric oxygen exposure during diving.
Ancienttrans-acting siRNAs Confer Robustness and Sensitivity onto the Auxin Response
2015-08-10

ABSTRACT Novel developmental programs often evolve via cooption of existing genetic networks. To understand this process, we explored cooption of the TAS3 tasiRNA pathway in the moss Physcomitrella patens . We find an ancestral function for this repeatedly redeployed pathway in the spatial regulation of a conserved set of Auxin Response Factors. In moss, this results in stochastic patterning of the filamentous protonemal tissue. Through modeling and experimentation, we demonstrate that tasiRNA regulation confers sensitivity and robustness onto the auxin response. Increased auxin sensitivity parallels increased developmental sensitivity to nitrogen, a key environmental signal. We propose that the properties lent to the auxin response network, along with the ability to stochastically modulate development in response to environmental cues, have contributed to the tasiRNA-ARF module’s repeated cooption during evolution. The signaling properties of a genetic network, and not just its developmental output, are thus critical to understanding the evolution of multicellular forms.
SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants
2015-08-11

Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites.
Diagnosis of Primary Hypophysitis in Germany
2015-08-11

Context: Representative data on diagnostic findings in primary hypophysitis (PrHy) are scarce. Objective: The objective of the study was to collate consistent data on clinical features in a large series of patients with PrHy. Another objective was to gain information on current practice in a diagnostic work-up. Design: The Pituitary Working Group of the German Society of Endocrinology conducted a nationwide retrospective cross-sectional cohort study in Germany. Patients: Seventy-six patients with PrHy were identified. Main Outcome Measures: Clinical and endocrinological features were assessed. Results: Headache (50%) and increase in body mass (18%) were the most frequent nonendocrine symptoms. Hypophysitis was associated with pregnancy in only 11% of the female patients. Diabetes insipidus was found in 54% of the patients at presentation. Hypogonadotropic hypogonadism was the most frequent endocrine failure (62%), whereas GH deficiency was the least frequent (37%). With 86%, thickening of the pituitary stalk was the prevailing neuroradiological sign. Compared with surgical cases, the cases without histological confirmation presented more often with suprasellar lesions and had less severe nonendocrine symptoms. Granulomatous hypophysitis was associated with more severe clinical symptoms than lymphocytic hypophysitis. Examination of cerebrospinal fluid was predominantly performed in participating neurosurgical centers, whereas thyroid antibodies were almost exclusively assessed in endocrinological centers. Conclusion: In contrast to the literature, hypogonadism was found to be the most frequent endocrine failure in PrHy. Weight gain was identified as a clinical sign of PrHy. In the majority of patients, PrHy can be reliably identified by characteristic clinical signs and symptoms, obviating histological confirmation. The diagnostic approach should be standardized in PrHy.
Diffusion imaging of nigral alterations in early Parkinson's disease with dopaminergic deficits
2015-08-11

ABSTRACT Background This study reports the baseline characteristics of diffusion tensor imaging data in Parkinson's disease (PD) patients and healthy control subjects from the Parkinson's Progression Markers Initiative. The main goals were to replicate previous findings of abnormal diffusion imaging values from the substantia nigra. in a large multicenter cohort and determine whether nigral diffusion alterations are associated with dopamine deficits. Methods Two hundred twenty subjects (PD = 153; control = 67) from 10 imaging sites were included. All subjects had a full neurological exam, a ( 123 I)ioflupane dopamine transporter (DAT) single‐photon emission computer tomography scan, and diffusion tensor imaging. Fractional anisotropy as well as radial and axial diffusivity was computed within multiple regions across the substantia nigra. Results A repeated‐measures analysis of variance found a marginally nonsignificant interaction between regional fractional anisotropy of the substantia nigra and disease status ( P = 0.08), conflicting with an earlier study. However, a linear mixed model that included control regions in addition to the nigral regions revealed a significant interaction between regions and disease status ( P = 0.002), implying a characteristic distribution of reduced fractional anisotropy across the substantia nigra in PD. Reduced fractional anisotropy in PD was also associated with diminished DAT binding ratios. Both axial and radial diffusivity were also abnormal in PD. Conclusions Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more‐sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality. © 2015 International Parkinson and Movement Disorder Society