julilili42/papers huggingface dataset:
Simultaneous Detection of Disseminated and Circulating Tumor Cells in Primary Breast Cancer Patients
2015-02-16

Our data confirm the prognostic relevance of DTCs and CTCs in patients with PBC. As we found no significant relationship between DTCs and CTCs, prospective trials should include their simultaneous detection. Within those trials, the question of whether or not DTCs and CTCs are independent subpopulations of malignant cell clones should be determined by molecular characterization.
Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI
2015-02-17

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.
Microvascular Complications in Childhood-Onset Type 1 Diabetes and Celiac Disease: A Multicenter Longitudinal Analysis of 56,514 Patients From the German-Austrian DPV Database
2015-02-17

OBJECTIVE To investigate whether celiac disease (CD) associated with type 1 diabetes increases the risk of microvascular complications. RESEARCH DESIGN AND METHODS Patients (n = 56,514) aged &amp;gt;10 years with diabetes duration &amp;lt;20 years from 392 centers in Germany and Austria were assigned to one of three categories (n): no CD (50,933), biopsy-confirmed CD (812), or suspected CD (4,769; clinical diagnosis or positive antibodies). The confirmed and suspected groups were combined and analyzed for retinopathy or nephropathy. Cox proportional hazards regression was used to adjust for potential confounders (glycated hemoglobin [HbA1c], age at diabetes onset, sex, smoking, dyslipidemia, and hypertension). RESULTS Kaplan-Meier analysis revealed that retinopathy and nephropathy occurred earlier in the presence versus absence of CD: retinopathy at age 26.7 years (95% CI 23.7–30.2) in 25% of patients with CD vs. age 33.7 years (33.2–34.4) in 25% without CD and microalbuminuria at age 32.8 years (29.7–42.5) vs. 42.4 years (41.4–43.3). The adjusted risk for both retinopathy (hazard ratio 1.263 [95% CI 1.078–1.481]) and nephropathy (1.359 [1.228–1.504]) was higher in patients with diabetes and CD versus those without CD. Cox regression revealed CD as an independent risk factor for microvascular complications after adjustment for confounders. CONCLUSIONS CD is an independent risk factor for retinopathy and nephropathy in patients with type 1 diabetes. Our study therefore supports the recommendation for regular serologic testing for CD, even in the absence of clinical CD. Further prospective studies are required to investigate whether a gluten-free diet might reduce the risk of microvascular disorders in patients with diabetes and CD.
A randomized, placebo‐controlled trial of AFQ056 for the treatment of chorea in Huntington's disease
2015-02-17

ABSTRACT Background This study investigated the hypothesis that AFQ056 (mavoglurant), a selective metabotropic glutamate receptor 5 antagonist, reduces chorea in Huntington's disease (HD). Methods This 32‐day randomized, double‐blind, parallel‐group, proof‐of‐concept study investigated AFQ056 (25‐150 mg [incremental doses], twice‐daily) versus placebo in patients with HD. Primary efficacy assessments were the chorea‐sum score and orientation index (nondominant hand) from the quantitative motor (Q‐Motor) grasping task at day 28. Key secondary efficacy assessments included finger‐tapping in the Unified Huntington's Disease Rating Scale–Total Motor Score and Q‐Motor measures. Safety and tolerability were assessed. Results Overall, 42 patients were randomized. At day 28, no improvement was observed on the primary efficacy assessments ( P &gt; 0.10) with AFQ056 versus placebo. The Q‐Motor speeded‐tapping interonset interval variability was reduced with AFQ056 versus placebo for the nondominant hand ( P = 0.01). The incidence of adverse events was 66.7% with AFQ056 and 57.1% with placebo. Conclusions AFQ056 did not reduce choreatic movements in HD, but was well tolerated. The clinical relevance of the Q‐Motor findings (speeded‐tapping) are unknown and may warrant further investigation. © 2015 International Parkinson and Movement Disorder Society
Galanin pathogenic mutations in temporal lobe epilepsy
2015-02-17

Temporal lobe epilepsy (TLE) is a common epilepsy syndrome with a complex etiology. Despite evidence for the participation of genetic factors, the genetic basis of TLE remains largely unknown. A role for the galanin neuropeptide in the regulation of epileptic seizures has been established in animal models more than two decades ago. However, until now there was no report of pathogenic mutations in GAL, the galanin-encoding gene, and therefore its role in human epilepsy was not established. Here, we studied a family with a pair of monozygotic twins affected by TLE and two unaffected siblings born to healthy parents. Exome sequencing revealed that both twins carried a novel de novo mutation (p.A39E) in the GAL gene. Functional analysis revealed that the p.A39E mutant showed antagonistic activity against galanin receptor 1 (GalR1)-mediated response, and decreased binding affinity and reduced agonist properties for GalR2. These findings suggest that the p.A39E mutant could impair galanin signaling in the hippocampus, leading to increased glutamatergic excitation and ultimately to TLE. In a cohort of 582 cases, we did not observe any pathogenic mutations indicating that mutations in GAL are a rare cause of TLE. The identification of a novel de novo mutation in a biologically-relevant candidate gene, coupled with functional evidence that the mutant protein disrupts galanin signaling, strongly supports GAL as the causal gene for the TLE in this family. Given the availability of galanin agonists which inhibit seizures, our findings could potentially have direct implications for the development of anti-epileptic treatment.
Next-Generation Sequencing Identifies Deregulation of MicroRNAs Involved in Both Innate and Adaptive Immune Response in ALK+ ALCL
2015-02-17

Anaplastic large cell lymphoma (ALCL) is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK). We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS). In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.
The benefit of repetitive skills training and frequency of expert feedback in the early acquisition of procedural skills
2015-02-18

Deliberate practice with both high- and low-frequency intermittent feedback results in a strong improvement of students' early procedural skill acquisition. High-frequency intermittent feedback, however, results in even better and smoother performance. We discuss the potential role of the cognitive workload on the results. We advocate a thoughtful allocation of tutor resources to future skills training.
Characterization of the E. coli proteome and its modifications during growth and ethanol stress
2015-02-18

We set out to provide a resource to the microbiology community especially with respect to systems biology based endeavors. To this end, we generated a comprehensive dataset monitoring the changes in protein expression, copy number, and post translational modifications in a systematic fashion during growth and ethanol stress in E. coli. We utilized high-resolution mass spectrometry (MS) combined with the Super-SILAC approach. In a single experiment, we have identified over 2300 proteins, which represent approximately 88% of the estimated expressed proteome of E. coli and estimated protein copy numbers using the Intensity Based Absolute Quantitation (iBAQ). The dynamic range of protein expression spanned up to six orders of magnitude, with the highest protein copy per cell estimated at approximately 300,000. We focused on the proteome dynamics involved during stationary phase growth. A global up-regulation of proteins related to stress response was detected in later stages of growth. We observed the down-regulation of the methyl directed mismatch repair system containing MutS and MutL of E. coli growing in long term growth cultures, confirming that higher incidence of mutations presents an important mechanism in the increase in genetic diversity and stationary phase survival in E. coli. During ethanol stress, known markers such as alcohol dehydrogenase and aldehyde dehydrogenase were induced, further validating the dataset. Finally, we performed unbiased protein modification detection and revealed changes of many known and unknown protein modifications in both experimental conditions. Data are available via ProteomeXchange with identifier PXD001648.
Experimental diagenesis of organo-mineral structures formed by microaerophilic Fe(II)-oxidizing bacteria
2015-02-18

Twisted stalks are organo-mineral structures produced by some microaerophilic Fe(II)-oxidizing bacteria at O2 concentrations as low as 3 μM. The presence of these structures in rocks having experienced a diagenetic history could indicate microbial Fe(II)-oxidizing activity as well as localized abundance of oxygen at the time of sediment deposition. Here we use spectroscopy and analytical microscopy to evaluate if--and what kind of--transformations occur in twisted stalks through experimental diagenesis. Unique mineral textures appear on stalks as temperature and pressure conditions increase. Haematite and magnetite form from ferrihydrite at 170 °C-120 MPa. Yet the twisted morphology of the stalks, and the organic matrix, mainly composed of long-chain saturated aliphatic compounds, are preserved at 250 °C-140 MPa. Our results suggest that iron minerals might play a role in maintaining the structural and chemical integrity of stalks under diagenetic conditions and provide spectroscopic signatures for the search of ancient life in the rock record.
Giant outburst from the supergiant fast X-ray transient IGR J17544−2619: accretion from a transient disc?
2015-02-18

Supergiant fast X-ray transients (SFXTs) are high mass X-ray binaries\\nassociated with OB supergiant companions and characterised by an X-ray flaring\\nbehaviour whose dynamical range reaches 5 orders of magnitude on timescales of\\na few hundred to thousands of seconds. Current investigations concentrate on\\nfinding possible mechanisms to inhibit accretion in SFXTs and explain their\\nunusually low average X-ray luminosity. We present the Swift observations of an\\nexceptionally bright outburst displayed by the SFXT IGR J17544-2619 on 2014\\nOctober 10 when the source achieved a peak luminosity of erg\\ns . This extends the total source dynamic range to 10 , the\\nlargest (by a factor of 10) recorded so far from an SFXT. Tentative evidence\\nfor pulsations at a period of 11.6 s is also reported. We show that these\\nobservations challenge, for the first time, the maximum theoretical luminosity\\nachievable by an SFXT and propose that this giant outburst was due to the\\nformation of a transient accretion disc around the compact object.\\n
One-Year Safety of Olodaterol Once Daily via Respimat® in Patients with GOLD 2–4 Chronic Obstructive Pulmonary Disease: Results of a Pre-Specified Pooled Analysis
2015-02-18

The novel long-acting β2-agonist olodaterol demonstrated an acceptable safety profile in short-term phase II clinical studies. This analysis of four randomized, double-blind, placebo-controlled, parallel-group, phase III studies (1222.11, NCT00782210; 1222.12, NCT00782509; 1222.13, NCT00793624; 1222.14, NCT00796653) evaluated the long-term safety of olodaterol once daily (QD) in a large cohort of patients with moderate to very severe (Global initiative for chronic Obstructive Lung Disease 2-4) chronic obstructive pulmonary disease (COPD). The studies compared olodaterol (5 or 10 μg) QD via Respimat®, formoterol 12 μg twice daily (BID) via Aerolizer® (1222.13 and 1222.14), and placebo for 48 weeks. Patients continued receiving background maintenance therapy, with ∼60% receiving concomitant cardiovascular therapy and 25% having a history of concomitant cardiac disease. Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring. In total, 3104 patients were included in the safety analysis: 876 received olodaterol 5 μg, 883 received olodaterol 10 μg, 885 received placebos, and 460 received formoterol 12 μg BID. Overall incidence of on-treatment AEs (71.2%), serious AEs (16.1%), and deaths (1.7%) were balanced across treatment groups. Respiratory and cardiovascular AEs, including major adverse cardiac events, were reported at similar frequencies in placebo and active treatment groups. The safety profiles of both olodaterol 5 μg (marketed and registered dose) and 10 μg QD delivered via Respimat® are comparable to placebo and formoterol BID in this population, with no safety signals identified.
Interstitial duplication of chromosome region 1q25.1q25.3: Report of a patient with mild cognitive deficits, tall stature and facial dysmorphisms
2015-02-18

Isolated interstitial duplications of chromosome band 1q25 are apparently very rare; no patients with detailed molecular and clinical characterization of duplications restricted to this region have been published to date. We report on a 9‐year‐old girl with mild cognitive deficits, tall stature, macrocephaly and discrete dysmorphic features in whom a de novo interstitial 7.5 Mb duplication of 1q25.1q25.3 was detected by SNP array analysis (arr[hg19] 1q25.1q25.3(173,925,505–181,381,242)x3 dn). The duplicated region was inversely inserted into chromosome band 1q42.2: 46,XX,der(1)(pter→q42.2::q25.3→q25.1::q42.2→qter). Overexpression of one or several of the 87 genes in the duplicated interval was presumably the major causative factor for the clinical manifestations. Reports of additional patients with overlapping duplications will be needed to establish detailed karyotype‐phenotype correlations and to gain a better understanding of the underlying pathomechanisms. © 2015 Wiley Periodicals, Inc.
Distinct Niemann-Pick Disease Type C Clinical, Cytological, and Biochemical Phenotype in an Adult Patient With 1 Mutated, OverexpressedNPC1Allele
2015-02-18

Abstract Niemann-Pick disease type C (NP-C) is a rare autosomal-recessive neurovisceral lysosomal storage disease. We report on a juvenile onset, now 25-year-old female patient with typical neurologic symptoms, including vertical gaze palsy, of NP-C. The diagnosis was supported by a positive filipin test (“variant biochemical phenotype” of cholesterol accumulation) in cultured fibroblasts, high numbers of “Niemann-Pick cells” in the bone marrow, and 1 positive out of 3 NP-C biomarkers tested, but NP-C was not definitely confirmed genetically. She showed only 1 known NPC1 variant (3 bp deletion in exon 18; p.N916del); this allele, however, being distinctly overexpressed at the messenger RNA level as compared to the wild-type allele, as a not as yet clarified (copathogenic?) phenomenon. The patient’s mother, also carrying the p.N916del allele but without overexpression, has a chronic inflammatory disease of the central nervous system classified as multiple sclerosis. However, her severe clinical phenotype includes some signs also consistent with NP-C. The laboratory diagnosis of NP-C can be challenging in detecting novel disease constellations.
Achieving Excellent Surgical Results in Vestibular Schwannoma Surgery from the Beginning. A Step-by-step Educational Approach in the 21st Century
2015-02-18

Objective: Vestibular schwannoma surgery requires a profound knowledge of anatomy and long-standing experience of surgical skull base techniques as patients nowadays requests high quality results from any surgeon from the beginning. This educes a dilemma for the young neurosurgeon as she/he is at the beginning of a learning curve. The presented series provides data that excellent results can be achieved from the beginning respecting carefully planned educational steps.
The influence of leaf litter diversity and soil fauna on initial soil erosion in subtropical forests
2015-02-19

Abstract Although the protective role of leaf litter cover against soil erosion is known for a long time, little research has been conducted on the processes involved. Moreover, the impact of soil meso‐ and macrofauna within the litter layer on erosion control is not clear. To investigate how leaf litter cover and diversity as well as meso‐ and macrofauna influence sediment discharge in subtropical forest ecosystems, a field experiment has been carried out in Southeast China. A full‐factorial random design with 96 micro‐scale runoff plots and 7 domestic leaf species was established and erosion was triggered by a rainfall simulator. Our results demonstrate that leaf litter cover protects soil from erosion (−82 % sediment discharge on leaf covered plots) by rainfall and this protection is removed as litter decomposes. The protective effect is influenced by the presence or absence of soil meso‐ and macrofauna. Fauna presence increases soil erosion rates significantly by 58 %, while leaf species diversity shows a non‐significant negative trend. We assume that the faunal effect arises from arthropods slackening and processing the soil surface as well as fragmenting and decomposing the protecting leaf litter covers. Even though the diversity level did not show a significant influence, single leaf species in monocultures show rather different impacts on sediment discharge and thus, erosion control. In our experiment, runoff plots with leaf litter from Machilus thunbergii showed the highest sediment discharge (68.0 g m −2 ) whereas plots with Cyclobalanopsis glauca showed the smallest rates (7.9 g m −2 ). Copyright © 2015 John Wiley &amp; Sons, Ltd.
Glucagon Cell Hyperplasia and Neoplasia With and Without Glucagon Receptor Mutations
2015-02-19

GCA with GCGR germline mutations seems to follow an autosomal-recessive trait. By interrupting the GCGR signaling pathways GCGR mutations probably cause GCA via glucagon cell hyperplasia. GCA also occurs in patients without GCGR mutations, but seems to be associated with fewer and smaller tumors.
Compact Superconducting Terahertz Source Operating in Liquid Nitrogen
2015-02-19

Sources of terahertz radiation (between the far infrared and microwave frequencies) are in high demand for a host of applications. The authors report on what is essentially a ``T-ray flashlight'', a compact and portable source of tunable, continuous terahertz light, employing a stack of intrinsic Josephson junctions in a cuprate superconductor as the emitter. This economical and convenient device can be driven by one everyday 1.5-V battery, and should facilitate airport security, nondestructive evaluation, and remote detection of trace gases, among other applications.
In vivo odourant response properties of migrating adult-born neurons in the mouse olfactory bulb
2015-02-19

Juxtaglomerular neurons (JGNs) of the mammalian olfactory bulb are generated throughout life. Their integration into the preexisting neural network, their differentiation and survival therein depend on sensory activity, but when and how these adult-born cells acquire responsiveness to sensory stimuli remains unknown. In vivo two-photon imaging of retrovirally labelled adult-born JGNs reveals that ~90% of the cells arrive at the glomerular layer after day post injection (DPI) 7. After arrival, adult-born JGNs are still migrating, but at DPI 9, 52% of them have odour-evoked Ca(2+) signals. Their odourant sensitivity closely resembles that of the parent glomerulus and surrounding JGNs, and their spontaneous and odour-evoked spiking is similar to that of their resident neighbours. Our data reveal a remarkably rapid functional integration of adult-born cells into the preexisting neural network. The mature pattern of odour-evoked responses of these cells strongly contrasts with their molecular phenotype, which is typical of immature, migrating neuroblasts.
Electronic structure at transition metal phthalocyanine-transition metal oxide interfaces: Cobalt phthalocyanine on epitaxial MnO films
2015-02-19

The electronic structure of the interface between cobalt phthalocyanine (CoPc) and epitaxially grown manganese oxide (MnO) thin films is studied by means of photoemission (PES) and X-ray absorption spectroscopy (XAS). Our results reveal a flat-lying adsorption geometry of the molecules on the oxide surface which allows a maximal interaction between the π-system and the substrate. A charge transfer from MnO, in particular, to the central metal atom of CoPc is observed by both PES and XAS. The change of the shape of N-K XAS spectra at the interface points, however, to the involvement of the Pc macrocycle in the charge transfer process. As a consequence of the charge transfer, energetic shifts of MnO related core levels were observed, which are discussed in terms of a Fermi level shift in the semiconducting MnO films due to interface charge redistribution.