julilili42/papers huggingface dataset:
Hybrid Off-pump Second-Stage Aortic Arch Repair after Type A Dissection
2018-09-22

Background Ascending aorta or hemi-arch repair are common in the acute phase of type A dissection. Postdissection aneurysms can develop with antegrade perfusion of the false lumen in the dissected aortic arch and require reoperation. Methods From 2012 to 2018, we reoperated nine patients with postdissection aneurysms using a hybrid technique without cardiopulmonary bypass. The patients had a EuroSCORE II of 13% and a logistic EuroSCORE I of 45% and were not candidates for frozen elephant trunk surgery. The median interval since the acute ascending repair was 184 (92; 528) days. All patients were treated by median resternotomy, ascending to carotid bypass on a partially clamped ascending graft, and transfemoral endovascular repair with a Relay NBS (nonbare stent) or conformable Gore C-TAG stent graft. Results Technical success was achieved in all cases. Mean follow-up was 405 (220; 672) days. There was no disabling stroke, endoleak, paraplegia, in-hospital, or late mortality. In all patients, the false lumen was completely thrombosed at the aortic arch level with a median aneurysm shrinkage of 13 mm in the distal arch. There was no bird beak or stent graft migration. Distal stent-induced new entry was observed in one case. Reinterventions were not necessary due to diameter stability. Conclusion Complete debranching with transfemoral thoracic endovascular aneurysm repair showed encouraging results in patients with relevant comorbidities. The used stent grafts performed well in the mid-term follow-up period with no endoleaks or migration.
Childhood supratentorial ependymomas with YAP1‐MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological features
2018-09-24

Abstract Ependymoma with YAP1‐MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1‐MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1‐MAMLD1 fusion was documented by RT‐PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity, presence of perivascular pseudo‐rosettes, small to medium‐sized nuclei with characteristic granular chromatin and strikingly abundant cells with dot‐like cytoplasmic expression of epithelial membrane antigen. Eleven cases presented features of anaplasia, corresponding to WHO grade III. MRI showed large supratentorial multinodular tumors with cystic components, heterogeneous contrast enhancement, located in the ventricular or periventricular region. One of two variants of YAP1‐MAMLD1 fusions was detected in all cases. The MIP genome profiles showed balanced profiles, with focal alterations of the YAP1 locus at 11q22.1–11q21.2 (7/14), MAMLD1 locus (Xp28) (10/14) and losses of chromosome arm 22q (5/14). Most patients were female (13/15) and younger than 3 years at diagnosis (12/15; median age, 8.2 months). Apart from one patient who died during surgery, all patients are alive without evidence of disease progression after receiving different treatment protocols, three without postoperative further treatment (median follow‐up, 4.84 years). In this to date, largest series of ependymomas with YAP1‐MAMLD1 fusions we show that they harbor characteristic histopathological, cytogenetic and imaging features, occur mostly in young girls under 3 years and are associated with good outcome. Therefore, this genetically defined neoplasm should be considered a distinct disease entity. The diagnosis should be confirmed by demonstration of the specific fusion. Further studies on large collaborative series are warranted to confirm our findings.
Optically Pumped Magnetometers for Magneto-Myography to Study the Innervation of the Hand
2018-09-24

The central nervous system exerts control over the activation of muscles via a dense network of nerve fibers targeting each individual muscle. There are numerous clinical situations where a detailed assessment of the nerve-innervation pattern is required for diagnosis and treatment. Especially, deep muscles are hard to examine and are as yet only accessible by uncomfortable and painful needle EMG techniques. Just recently, a new and flexible method and device became available to measure the small magnetic fields generated by the contraction of the muscles: optically pumped magnetometers (OPMs). OPMs are small devices that measure the zero-field level crossing resonance of spin-polarized rubidium atoms. The resonance is dependent on the local magnetic field strength, and therefore, these devices are able to measure small magnetic fields in the range of a few hundred femtoteslas. In this paper, we demonstrate as a proof of principle that OPMs can be used to measure the low magnetic fields generated by small hand muscles after electric stimulation of the ulnar or median nerve. We show that using this technique, we are able to record differential innervation pattern of small palmar hand muscles and are capable of distinguishing between areas innervated by the median or ulnar nerve. We expect that the new approach will have an important impact on the diagnosis of nerve entrapment syndromes, spinal cord lesions, and neuromuscular diseases.
DNA methylation of neural EGFL like�1 (NELL1) is associated with advanced disease and the metastatic state of renal cell cancer patients
2018-09-24

Recent studies have shown that NELL1 expression is silenced epigenetically in human renal cell cancer (RCC) tissues and in RCC cell lines. However, it remains unknown whether NELL1 promoter methylation observed in clinical specimens might be associated with the clinicopathology or survival of patients with RCC. We analyzed NELL1 DNA methylation in tissues from patients with RCC and in adjacent normal renal tissues. In addition, we evaluated NELL1 methylation in cell lines derived from different urogenital tumors (prostate cancer, urothelial cancer and RCC). We performed regression analyses to determine whether NELL1 methylation is associated with clinicopathological parameters and recurrence‐free survival (RFS). This cross‐sectional study included 98 patients with RCC and 63 paired tumor and adjacent normal tissue samples. We analyzed a locus in the intron 1 region of NELL1 with pyrosequencing. We performed in silico analysis of NELL1 methylation in the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) data set (n=284 patients), which served as a validation study. Statistical analyses were performed with the two‐sided paired t‐test for paired tumor and adjacent normal samples. We used logistic regression for subgroup comparisons and Cox regression for RFS comparisons. The mean methylation level was 6.8% higher in RCC tissues compared to paired adjacent normal tissues (paired t‐test, P<0.001). Methylation levels in RCC were associated with advanced disease (P=0.002), the presence of distant metastases (P=0.004), and shorter RFS (P=0.035, HR: 4.15). In silico validation with TCGA KIRC data for adjacent loci also demonstrated that high relative methylation levels were associated with adverse clinicopathology and shortened RFS. Our results suggest that NELL1 methylation contributes to RCC disease progression. This finding could provide a clinical marker to complement recent functional analyses in tumor models.
Regulation of the Natriuretic Peptide Receptor 2 (Npr2) by Phosphorylation of Juxtamembrane Serine and Threonine Residues Is Essential for Bifurcation of Sensory Axons
2018-09-24

cGMP signaling elicited by activation of the transmembrane receptor guanylyl cyclase Npr2 (also known as guanylyl cyclase B) by the ligand CNP controls sensory axon bifurcation of DRG and cranial sensory ganglion (CSG) neurons entering the spinal cord or hindbrain, respectively. Previous studies have shown that Npr2 is phosphorylated on serine and threonine residues in its kinase homology domain (KHD). However, it is unknown whether phosphorylation of Npr2 is essential for axon bifurcation. Here, we generated a knock-in mouse line in which the seven regulatory serine and threonine residues in the KHD of Npr2 were substituted by alanine (Npr2-7A), resulting in a nonphosphorylatable enzyme. Real-time imaging of cGMP in DRG neurons with a genetically encoded fluorescent cGMP sensor or biochemical analysis of guanylyl cyclase activity in brain or lung tissue revealed the absence of CNP-induced cGMP generation in the Npr2 7A/7A mutant. Consequently, bifurcation of axons, but not collateral formation, from DRG or CSG in this mouse mutant was perturbed at embryonic and mature stages. In contrast, axon branching was normal in a mouse mutant in which constitutive phosphorylation of Npr2 is mimicked by a replacement of all of the seven serine and threonine sites by glutamic acid (Npr2–7E). Furthermore, we demonstrate that the Npr2 7A/7A mutation causes dwarfism as described for global Npr2 mutants. In conclusion, our in vivo studies provide strong evidence that phosphorylation of the seven serine and threonine residues in the KHD of Npr2 is an important regulatory element of Npr2-mediated cGMP signaling which affects physiological processes, such as axon bifurcation and bone growth. SIGNIFICANCE STATEMENT The branching of axons is a morphological hallmark of virtually all neurons. It allows an individual neuron to innervate different targets and to communicate with neurons located in different regions of the nervous system. The natriuretic peptide receptor 2 (Npr2), a transmembrane guanylyl cyclase, is essential for the initiation of bifurcation of sensory axons when entering the spinal cord or the hindbrain. By using two genetically engineered mouse lines, we show that phosphorylation of specific serine and threonine residues in juxtamembrane regions of Npr2 are required for its enzymatic activity and for axon bifurcation. These investigations might help to understand the regulation of Npr2 and its integration in intracellular signaling systems.
[Ge9{Si(SiMe3)3}2{Ge(SiMe3)3}]–: The Mixed Substituted Metalloid Germanium Cluster and the Intermetalloid Cluster [ZnGe18{Si(SiMe3)3}4{Ge(SiMe3)3}2]
2018-09-24

The novel metalloid germanium cluster [Ge 9 (Hyp) 2 Hyp Ge ] – ( 1 ) was synthesized, exhibiting two different bulky groups [Hyp = Si(SiMe 3 ) 3 ; Hyp Ge = Ge(SiMe 3 ) 3 ]. Further reaction of 1 with ZnCl 2 gives the derivative [ZnGe 18 (Hyp) 4 (Hyp Ge ) 2 ] ( 2 ) in good yield, showing that the substitution of Si(SiMe 3 ) 3 by Ge(SiMe 3 ) 3 within a metalloid Ge 9 R 3 – compound leads to a comparable reactivity. 1 and 2 are characterized by NMR spectroscopy, mass spectrometry ( 1 ) and single crystal structure analyses ( 2 ). 1 and 2 are the first metalloid germanium clusters bearing germyl groups.
Electronically Coupled, Two-Dimensional Assembly of Cu1.1S Nanodiscs for Selective Vapor Sensing Applications
2018-09-24

We study temperature-dependent charge transport in two-dimensional assemblies of copper sulfide nanodiscs in the covellite crystal phase (Cu1.1S). To enhance interparticle coupling, we cross-link the nanocrystals with the organic π-system Cu-4,4′,4′′,4′′′-tetraaminophthalocyanine and observe an increase in the conductivity by 6 orders of magnitude. The electrical properties of monolayers of this hybrid ensemble are consistent with a two-dimensional semiconductor and exhibit two abrupt changes at discrete temperatures (120 and 210 K), which may be interpreted as phase changes. X-ray scattering experiments serve to study the importance of electronic conjugation in the organic π-system vs interparticle spacing for efficient charge transport. Applying the hybrid ensemble as a chemiresistor in organic vapor sensing experiments reveals a strong selectivity between polar and nonpolar analytes, which we discuss in light of the role of the organic π-system and its metal center.
Unusual high blood glucose in ketoacidosis as first presentation of type 1 diabetes mellitus
2018-09-24

Summary Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH &lt;7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy. Learning points: Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients. Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes. First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes. Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis. In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.
Role of the stratospheric chemistry-climate interactions in the hotclimate conditions of the Eocene
2018-09-24

Abstract. The stratospheric ozone layer plays a key role in atmospheric thermal structure and circulation. Although stratospheric ozone distribution is sensitive to changes in composition and climate, the modifications of stratospheric ozone are not usually considered in climate studies at geological time scales. Here, we evaluate with a chemical-climate model the potential role of stratospheric ozone chemistry in the case of the Eocene hot conditions. We show that the structure of the ozone layer is significantly different under these conditions (4×CO2 climate and high concentrations of tropospheric N2O and CH4). While at mid and high latitudes, the total column ozone is found to be enhanced, the tropical ozone column remains more or less unchanged. These ozone changes are related to the stratospheric cooling and an acceleration of stratospheric Brewer-Dobson circulation simulated under Eocene climate. The meridional distribution of the total ozone column appears also to be strongly modified, showing particularly pronounced mid-latitudes maxima and steeper negative poleward gradient from these maxima. These anomalies are consistent with changes in the seasonal evolution of the polar vortex during the winter, especially in the Northern Hemisphere. Compared to a pre-industrial atmospheric composition, the changes in local ozone concentration reach up to 40 % for zonal annual mean and affect temperature by a few Kelvins in the middle stratosphere. As inter-model differences in simulating the deep past temperatures are quite high, the consideration of atmospheric chemistry, which is computationally demanding in Earth system models, may seem superfluous. However, our results suggest that using stratospheric ozone calculated by the model (and hence more physically consistent with Eocene conditions) instead of the commonly specified preindustrial ozone distribution can change the simulated global surface air temperature by 14 %. This error is of the same order as the effect of non-CO2 boundary conditions (topography, bathymetry, solar constant &amp;amp; vegetation). Moreover, the results highlight the sensitivity of stratospheric ozone to hot climate conditions. Since the climate sensitivity to stratospheric ozone feedback largely differs between models, it must be better constrained not only for deep past conditions but also for future climates.
Comparing Arabidopsis receptor kinase and receptor protein‐mediated immune signaling reveals BIK1‐dependent differences
2018-09-25

Summary Pattern recognition receptors (PRRs) sense microbial patterns and activate innate immunity against attempted microbial invasions. The leucine‐rich repeat receptor kinases (LRR‐RK) FLS2 and EFR, and the LRR receptor protein (LRR‐RP) receptors RLP23 and RLP42, respectively, represent prototypical members of these two prominent and closely related PRR families. We conducted a survey of Arabidopsis thaliana immune signaling mediated by these receptors to address the question of commonalities and differences between LRR‐RK and LRR‐RP signaling. Quantitative differences in timing and amplitude were observed for several early immune responses, with RP‐mediated responses typically being slower and more prolonged than those mediated by RKs. Activation of RLP23, but not FLS2, induced the production of camalexin. Transcriptomic analysis revealed that RLP23‐regulated genes represent only a fraction of those genes differentially expressed upon FLS2 activation. Several positive and negative regulators of FLS2‐signaling play similar roles in RLP23 signaling. Intriguingly, the cytoplasmic receptor kinase BIK1, a positive regulator of RK signaling, acts as a negative regulator of RP‐type immune receptors in a manner dependent on BIK1 kinase activity. Our study unveiled unexpected differences in two closely related receptor systems and reports a new negative role of BIK1 in plant immunity.
Optimization of Nutrition Therapy with the Use of Calorimetry to Determine and Control Energy Needs in Mechanically Ventilated Critically Ill Patients: The ONCA Study, a Randomized, Prospective Pilot Study
2018-09-25

Abstract Background Adequate nutrition therapy in critically ill patients poses a challenge because of the variable energy and substrate needs. The objective was to investigate whether nutrition therapy involving indirect calorimetry (IC), instead of equations for assessment of energy needs, could improve the nutrition status of critically ill patients. Methods Forty mechanically ventilated patients were randomized into a group in which energy needs were controlled by calorimetry (IC group) and a group treated with a formula‐based approach reflecting standard care (SC group). The primary outcome was change in the phase angle (PhA), a bioelectrical impedance parameter related to nutrition status and prognosis. Results The mean IC‐based energy requirement was lower than the formula‐based estimate (21.1 ± 6.4 versus [vs] 25 kcal/kg/d, P &lt; .01). The IC group reached 98% ± 8% of the energy goal, whereas the SC group reached only 79% ± 29% ( P &lt; 0.05), although mean intake was similar in both groups. The protein intake goal was better met in the IC group (91% ± 24%) than the SC group (73% ± 33%). The PhA of the IC group did not change during treatment, whereas that of the SC group tended to decrease by 0.36° ± 0.86° ( P = .077). A shorter length of stay in intensive care was observed in the IC than in the SC group (13 ± 8 vs 24 ± 20 days, P &lt; .05). Conclusion Intensified individual nutrition therapy involving IC appears to be useful for improving nutrition status in critically ill patients.
Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease
2018-09-25

Abstract Introduction Little is known about effects of physical activity (PA) in genetically driven early‐onset autosomal dominant Alzheimer's disease (AD). Methods A total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross‐sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations. Results Mutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD‐like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers. Discussion These results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.
Arabidopsis RUP2 represses UVR8-mediated flowering in noninductive photoperiods
2018-09-25

Plants have evolved complex photoreceptor-controlled mechanisms to sense and respond to seasonal changes in day length. This ability allows plants to optimally time the transition from vegetative growth to flowering. UV-B is an important part intrinsic to sunlight; however, whether and how it affects photoperiodic flowering has remained elusive. Here, we report that, in the presence of UV-B, genetic mutation of REPRESSOR OF UV-B PHOTOMORPHOGENESIS 2 ( RUP2 ) renders the facultative long day plant Arabidopsis thaliana a day-neutral plant and that this phenotype is dependent on the UV RESISTANCE LOCUS 8 (UVR8) UV-B photoreceptor. We provide evidence that the floral repression activity of RUP2 involves direct interaction with CONSTANS, repression of this key activator of flowering, and suppression of FLOWERING LOCUS T transcription. RUP2 therefore functions as an essential repressor of UVR8-mediated induction of flowering under noninductive short day conditions and thus provides a crucial mechanism of photoperiodic flowering control.
How to train your syllable stress awareness - A digital game-based intervention for German dyslexic children
2018-09-25

Developmental dyslexia is one of the most frequent learning disorders and affects 4-10 % of the German population. The learning disorder affects educational, personal, and social development of children in a negative way. We examine three different approaches to treat learning disorders. That is, therapeutic, computer-based, and digital game-based interventions. We reflect on the advantages and disadvantages of these approaches that have been shown to be supportive for dyslexic primary-school children. Our literature review shows that there is a lack of digital game-based interventions for the treatment of spelling disorders. To fill this gap, we propose such a mobile serious game which uses evidence-based trainings and introduces novel features in order to help dyslexic children to improve their reading and spelling performance. We propose an intervention to train awareness of syllable stress and explore the innovative use of mouth motor activities and embodied trainings. To conclude, we suggest that, in addition to traditional approaches, digital-game based approaches should be used supplementary to (re-) engage and motivate learners.