julilili42/papers huggingface dataset:
The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans
2017-11-14

The liver is a central regulator of whole body glucose, and lipid homeostasis and hepatokines, like fetuin-A, have been identified as markers and mediators of fatty liver-induced cardiometabolic risk. The closely related protein fetuin-B was shown to be upregulated in the fatty liver and to impact on glucose homeostasis in mice. In the present study we aimed to test the relevance of these findings in humans. In 55 subjects, hepatic mRNA expression of both hepatokines, fetuin-A and fetuin-B, associated positively with liver triglyceride content, whereas only fetuin-A expression associated with the homeostatic model assessment of insulin resistance. In 220 subjects who underwent precise metabolic phenotyping, circulating fetuin-A, but not fetuin-B, associated positively with liver fat content, and negatively with insulin sensitivity, measured during the oral glucose tolerance test (OGTT) and during the euglycemic, hyperinsulinemic clamp. Both circulating fetuin-A and fetuin-B correlated positively with the glucose area under the curve during the OGTT, but after additional adjustment for insulin sensitivity this relationship remained significant only for fetuin-B. In conclusion, despite the fact that the two hepatokines, fetuin-A and fetuin-B, are upregulated in the state of hepatic steatosis in humans, it appears that they differently impact on glucose homeostasis. Our data are in agreement with observations that fetuin-A can alter insulin signaling and that fetuin-B may regulate glucose homeostasis via so far unknown effects, possibly on glucose effectiveness.
drLumi: An open-source package to manage data, calibrate, and conduct quality control of multiplex bead-based immunoassays data analysis
2017-11-14

Multiplex bead-based immunoassays are used to measure concentrations of several analytes simultaneously. These assays include control standard curves (SC) to reduce between-plate variability and normalize quantitation of analytes of biological samples. Suboptimal calibration might result in large random error and decreased number of samples with analyte concentrations within the limits of quantification. Suboptimal calibration may be a consequence of poor fitness of the functions used for the SC, the treatment of the background noise and the method used to estimate the limits of quantification. Currently assessment of fitness of curves is largely dependent on operator and that may add additional error. Moreover, there is no software to automate data managing and quality control. In this article we present a R package, drLumi, with functions for managing data, calibrating assays and performing quality control. To optimize the assay the package implements: i) three dose-response functions, ii) four approaches for treating background noise and iii) three methods for estimating limits of quantifications. Other implemented functions are focused on the quality control of the fitted standard curve: detection of outliers, estimation of the confidence or prediction interval, and estimation of summary statistics. With demonstration purpose, we apply the software to 30 cytokines, chemokines and growth factors measured in a multiplex bead-based immunoassay in a study aiming to measure correlates of risk or protection from malaria of the RTS,S malaria vaccine nested in the Phase 3 randomized controlled trial of this vaccine.
Stage 1 Registered Report: Effect of deficient phagocytosis on neuronal survival and neurological outcome after temporary middle cerebral artery occlusion (tMCAo)
2017-11-14

<ns4:p>Stroke is a major cause of death and disability worldwide. In addition to neuronal death resulting directly from energy depletion due to lack of blood supply, inflammation and microglial activation following ischemic brain injury has been increasingly recognized to be a key contributor to the pathophysiology of cerebrovascular disease. However, our understanding of the cross talk between the ischemic brain and the immune system is limited. Recently, we demonstrated that following focal ischemia, death of mature viable neurons can be executed through phagocytosis by microglial cells or recruited macrophages, i.e. through phagoptosis. It was shown that inhibition of phagocytic signaling pathways following endothelin-1 induced focal cerebral ischemia leads to increased neuronal survival and neurological recovery. This suggests that inhibition of specific phagocytic pathways may prevent neuronal death during cerebral ischemia. To further explore this potential therapeutic target, we propose to assess the role of phagocytosis in an established model of temporary (45min) middle cerebral artery occlusion (tMCAo), and to evaluate neuronal survival and neurological recovery in mice with deficient phagocytosis. The primary outcome of this study will be forelimb function assessed with the staircase test. Secondary outcomes constitute Rotarod performance, stroke volume (quantified on MR imaging or brain sections, respectively), diffusion tensor imaging (DTI) connectome mapping, and histological analyses to measure neuronal and microglial densities, and phagocytic activity. Male mice aged 10-12 weeks will be used for experiments.</ns4:p>
Brain-derived neurotrophic factor (BDNF) as a potential biomarker for resting-state network remodeling after ketamine infusion
2017-11-14

Introduction Ketamine, an NMDAR antagonist, produces fast antidepressant response with a maximum efficacy 24h after infusion [1]. Animal studies showed that ketamine generates higher synaptic plasticity via induction of Brain-derived neurotrophic factor (BDNF) [2]. Patients with depression have lower blood level of BDNF and show an increase after ketamine infusion [4]. Besides, depressed patients have hyperconnectivity within the Default mode network (DMN) [5]. Ketamine decreases the Functional Connectivity (FC) in healthy subjects between posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC), two main regions within DMN [6], revealing possible mechanisms of the antidepressant effect. Methods In a double-blind study, 81 healthy subjects received infusion of either ketamine (0.5 mg/kg) or saline. In each subject, resting state fMR images (TR= 2.8s, voxel size= 2 × 2 × 2 mm3, 7T ) and plasma blood samples were acquired at baseline and 24h post-infusion. Ketamine (n=32) and placebo (n=30) groups were preprocessed using scripts developed in the functional connectome 1000 project. Dorsal PCC (dPCC) was chosen as a priori seed region [6] and FC maps were calculated. The mean FC value was extracted from clusters showing significant change after infusion. Extracted FC values were correlated with the plasma BDNF at 24h (n=45). Results 24h after infusion, ketamine treated subjects showed higher BDNF level compared to placebo (p=0.015). A decrease in FC between the dPCC and both dorsolateral PFC (p=0.005 FWE) and two cluster in mPFC (p=0.001 p=0.030 FWE) was observed 24h after infusion. Subjects with higher BDNF level after ketamine show significantly higher FC disconnection between dorsal PCC and mPFC (r= 0.64, p=0.006). Conclusions Ketamine decreases FC within the DMN and increases BDNF 24h after ketamine. Higher BDNF level correlates with stronger FC disconnection between anterior (mPFC) and posterior (dPCC) part of DMN. This finding highlights the role of BDNF as a potential biomarker for network remodeling in the brain. 1 Zarate et al. (2006) A Randomized Trial of an N-methyl-D- aspartate Antagonist in Treatment-Resistant Major Depression. 2 Duman et al. (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. 3 Haile (2013) Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. 4 Kaiser et al. (2015). Large-scale network dysfunction in major depressive disorder. 5 Scheidegger et al. (2012). Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.
A highly asynchronous developmental program triggered during germination of dormant akinetes of filamentous diazotrophic cyanobacteria
2017-11-15

Germination of akinetes of filamentous heterocyst-forming cyanobacteria of the order Nostocales is an essential process that ensures survival and recolonization after long periods of unfavorable conditions, as desiccation, cold and low light. We studied the morphological, physiological and metabolic changes that occur during germination of akinetes in two model species of cell differentiation, Anabaena variabilis ATCC 29413 and Nostoc punctiforme ATCC 29133, which live in different habitats. We characterized the akinete envelopes and showed their similarity to envelopes of N2-fixing heterocysts. Akinete germination started inside the envelopes and was dependent on light intensity but independent of nitrogen supply. During the germination of A. variabilis akinetes, cell division and heterocyst differentiation were highly accelerated. The energy for cell division was initially supplied by respiration of glycogen and subsequently by photosynthesis. By contrast, during germination of N. punctiforme akinetes, cell division and heterocyst differentiation were slow. During the initial 15-20 h, N. punctiforme akinetes increased in volume and some burst. Only then did intact akinetes start to divide and fully germinate, possibly fueled by nutrients released from dead akinetes. The different strategies used by these different cyanobacteria allow successful germination of dormant cells and recolonization under favorable conditions.
Sleep increases explicit solutions and reduces intuitive judgments of semantic coherence
2017-11-15

Sleep fosters the generation of explicit knowledge. Whether sleep also benefits implicit intuitive decisions about underlying patterns is unclear. We examined sleep's role in explicit and intuitive semantic coherence judgments. Participants encoded sets of three words and after a sleep or wake period were required to judge the potential convergence of these words on a common fourth associate. Compared with wakefulness, sleep increased the number of explicitly named common associates and decreased the number of intuitive judgments. This suggests that sleep enhances the extraction of explicit knowledge at the expense of the ability to make intuitive decisions about semantic coherence.
The family narratives of three siblings living in a ‘street situation’ since birth
2017-11-15

The spontaneous narratives of three brothers, ages 5, 8, and 11, in response to a structured story stem task were analysed for representations of positive and negative family interactions. The children had lived their entire lives with no permanent home, and often on the streets, in the care of their mother. The story stem task presented brief scenarios of parent and family conflict and a child's need for comfort. Analyses revealed children's understanding of basic family role structures; yet, their narratives were also characterized by emotional detachment, limited parental engagement, and self-centredness. Implications for young children's coping with great adversity are discussed.
S118 Elk1 gene deletion leads to spontaneous early fibrotic changes in the ageing lung
2017-11-15

&lt;sec&gt;&lt;st&gt;Rationale&lt;/st&gt; Idiopathic pulmonary fibrosis is a chronic fibroproliferative disease with a median survival of approximately 3 years. αvβ6 integrins are upregulated in lung fibrosis and are associated with increased activation of the profibrotic cytokine TGF-β. The transcription factor Elk1 can repress gene expression of β6. We therefore hypothesise that animals lacking functional Elk1 (&lt;it&gt;Elk1-/0 &lt;/it&gt;) will develop age related pulmonary fibrosis. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Methods&lt;/st&gt; Elk1 knock-out (&lt;it&gt;Elk1-/0 &lt;/it&gt;) and wild-type (&lt;it&gt;Elk1+/0 &lt;/it&gt;) mice were allowed to age for 365 days. At 365 days old mice were sacrificed and their lungs harvested for evaluation of collagen gene expression, lung hydroxyproline concentration and histological assessment. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Results&lt;/st&gt; Lungs were extracted and lung wet weights were measured in &lt;it&gt;Elk1-/0 &lt;/it&gt; mice and wild-type (&lt;it&gt;Elk1+/0 &lt;/it&gt;) controls and no significant difference between the two genotypes was shown (175.7 mg, 161.8 mg respectively n=6–8). However, assessment of total lung hydroxyproline established that there was significantly more hydroxyproline in &lt;it&gt;Elk1-/0 &lt;/it&gt; mice compared with &lt;it&gt;Elk1+/0 &lt;/it&gt; controls (852.3, 758.4 μg/lung set, respectively, n=5–8, p=0.0346). Assessment of Masson’s trichrome stained &lt;it&gt;Elk1-/0 &lt;/it&gt; lung tissue sections found a small number of fibrotic lesions were present. Furthermore, there was a trend towards increased alveolar wall median thickness in &lt;it&gt;Elk1-/0 &lt;/it&gt; mice compared with &lt;it&gt;Elk1+/0 &lt;/it&gt; animals (5.94 vs 5.56 μm respectively). In a small number of 12 week old mice we identified a trend towards increased α-smooth muscle actin (αSMA) mRNA expression in the lungs of &lt;it&gt;Elk1-/0 &lt;/it&gt; mice compared with &lt;it&gt;Elk1+/0 &lt;/it&gt; controls (9.40, 2.24 median relative expression, respectively n=3). We therefore performed immunohistochemical staining for αSMA in the lungs of mice aged to 1 year and demonstrated visible increases in expression of αSMA in the alveolar epithelium of &lt;it&gt;Elk1-/0 &lt;/it&gt; mice but not in &lt;it&gt;Elk1+/0 &lt;/it&gt; controls. &lt;/sec&gt; &lt;sec&gt;&lt;st&gt;Conclusion&lt;/st&gt; These data suggest that Elk1 gene deletion result in age-related early fibrotic changes associated with the development of pulmonary fibrosis. &lt;/sec&gt;
Testing the Kerr paradigm with the black hole shadow
2017-11-16

Within 5-10 years, submillimeter VLBI facilities will be hopefully able to\\nimage the "shadow" of SgrA . When a black hole is surrounded by an optically\\nthin emitting medium, the boundary of the shadow corresponds to the apparent\\nphoton capture sphere and only depends on the background metric. An accurate\\ndetermination of the shape of the shadow of SgrA could constrain possible\\ndeviations from the Kerr solution. In combination with other measurements,\\nthese observations could test the Kerr black hole paradigm.\\n
2‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles: An Overview on Synthetic Strategies and Biological Activity
2017-11-16

2‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles represent an important class of ATP‐competitive protein kinase inhibitors, offering the possibility of multiple interactions with different regions of the target enzyme. The necessity of exploring the effects of diverse chemical decorations around the imidazole core prompted the design of several synthetic routes aimed at achieving both efficiency and flexibility. Additionally, the optimization of established protocols and the extensive use of transition metal‐catalyzed cross‐coupling reactions have been broadening the spectrum of preparative methodologies within the last decade. This review summarizes the progress in the development of synthetic strategies leading to 2‐alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles and 1‐alkyl‐2‐alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles and offers a glance at the biological activities of this class of compounds.
Two novel families with hemiplegic migraine caused by recurrent SCN1A mutation p.F1499L
2017-11-16

Background Familial hemiplegic migraine type 3 is a monogenic subtype of migraine caused by missense mutations in the neuronal voltage-gated sodium channel gene SCN1A, with 10 different mutations reported so far. In two familial hemiplegic migraine type 3 families, partial cosegregation with a rare eye phenotype (elicited repetitive daily blindness) was previously reported. Methods Two novel familial hemiplegic migraine pedigrees were subjected to genetic analysis and detailed work-up of associated clinical features. Results In both pedigrees, we identified SCN1A mutation p.F1499L, which has been previously associated with familial hemiplegic migraine type 3 and elicited repetitive daily blindness. Both families displayed a pure familial hemiplegic migraine phenotype without evidence of an episodic eye phenotype. Conclusion Like a substantial proportion of other familial hemiplegic migraine type 3 mutations, p.F1499L affects the intracellular linker between domains III and IV of SCN1A, which seems to be a mutational hot-spot. Our new data establish p.F1499L as a recurrent familial hemiplegic migraine type 3 mutation. Elicited repetitive daily blindness seems to be a rare phenomenon in familial hemiplegic migraine type 3, even in carriers of the same mutation.
Development and Validation of an Ultrasensitive Procalcitonin Sandwich Immunoassay
2017-11-16

Procalcitonin (PCT) is well established as a highly specific biomarker for the detection of bacterial infections and sepsis. However, the currently available diagnostic tests are not able to detect very low or very early increases of PCT or even baseline levels in healthy individuals or patients with non-bacterial infections. In order to be able to detect these very low concentrations of PCT, a sandwich immunoassay was developed using high sensitivity Single Molecule Array technology (Simoa). The assay was thoroughly validated and applied to analyze human cerebrospinal fluid (CSF) and serum samples from patients with bacterial or viral meningitis as well as CSF, serum, and K2 EDTA plasma from healthy control subjects. A 50-fold increase in sensitivity compared to the current gold standard assays was achieved, which was sensitive enough for the detection of baseline PCT levels. Both serum and CSF showed significantly elevated PCT levels in patients with bacterial meningitis compared to patients with viral meningitis and the healthy control group. Procalcitonin concentration levels for patients with viral meningitis and the control group could be measured, but were not significantly different. The determination of PCT in the low pg·mL−1 range could help to improve the monitoring of bacterial infectious diseases, as PCT level changes could be detected earlier.
Severe cardiovascular involvement in Hughes-Stovin syndrome
2017-11-16

Hughes-Stovin syndrome (HSS) is a rare autoimmune vasculitis and is characterized by the simultaneous presence of deep venous thrombosis and pulmonary artery aneurysms. The exact etiology and pathogenesis of this life-threatening syndrome is currently unknown. The disease is thought to be a variant of Behcet’s disease with major vascular involvement. Here we report a case of a 19-year-old man from West Africa with a severe cardiovascular manifestation of HSS. The patient was referred to our hospital with dyspnoea, recurrent fever and swelling of the left leg. Echocardiography revealed extensive biventricular thrombi. He responded very well to immunosuppressive therapy in combination with anticoagulation using low-molecular-weight heparins (LMWHs). Thrombolysis was consciously avoided.
Recent progress on the tidal deformability of spinning compact objects
2017-11-16

We give a short review on recent progress in the theory of tidal deformability of a slowly spinning compact object. A rotating object immersed in a quadrupolar, electric tidal field can acquire some induced mass, spin, quadrupole, octupole and hexadecapole moments to second order in the spin. Angular momentum introduces couplings between electric and magnetic distortions and new classes of spin-induced, tidal Love numbers emerge. All tidal Love numbers of a Kerr black hole were proved to be exactly zero to first order in the spin and also to second order in the spin, at least in the axisymmetric case. The tidal Love numbers of a neutron star depend strongly on the equation of state. Spin-tidal couplings deteriorate some approximate universal relations that exist for neutron stars in the static case. For a binary system close to the merger, various components of the tidal field become relevant. Preliminary results suggest that spin-tidal couplings can introduce important corrections to the gravitational waveforms of spinning neutron-star binaries approaching the merger.
Testing the Kerr paradigm with X-ray observations
2017-11-16

Astrophysical black hole candidates are thought to be the Kerr black holes of\\ngeneral relativity, but the actual nature of these objects has still to be\\nconfirmed. The continuum-fitting and the iron line methods are currently the\\nonly available techniques to probe the spacetime geometry around these bodies\\nand test the Kerr black hole paradigm. The continuum-fitting method is a robust\\napproach, but the shape of the disk's thermal spectrum is in general too simple\\nto measure the spin and to constrain possible deviations from the Kerr solution\\nat the same time. The iron line analysis is potentially a powerful technique,\\nbut at the moment we do not have high quality data and a robust astrophysical\\nmodel.\\n
Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma
2017-11-17

Key Points Rd continuous significantly extended OS compared with MPT and resulted in comparable OS to that with Rd18 in patients with multiple myeloma. Patients achieving complete or very good partial response with Rd benefited greatly from continuous vs fixed treatment in terms of PFS.
Total evidence analysis and body size evolution of extant and extinct tortoises (Testudines: Cryptodira: Pan‐Testudinidae)
2017-11-17

Abstract Testudinidae (tortoises) is an extant clade of terrestrial turtles of worldwide distribution and with a rich fossil record that provides an exceptional context for studying their evolutionary history. Because of the lack of global phylogenetic analyses integrating extinct taxa, our current knowledge of the relationships of the total clade of Testudinidae is rather poor. To resolve this issue, we performed the first total evidence analysis of Pan‐Testudinidae. The total evidence trees are congruent with the molecular topology and agree on the dichotomy of derived Testudinidae (=Testudininae; Converted Clade Name) into two previously recognized major clades, Testudona and Geochelona (New Clade Name). The integration of extinct taxa into the analysis allowed the stratigraphic fit of the total evidence trees, indicating that crown Testudininae, Testudona and Geochelona all originated by the Late Eocene, in agreement with recent molecular estimates. Ghost lineage analysis indicates high diversification in the Late Eocene and in the Miocene. The age of crown Testudo is Late Miocene, again in accordance with some molecular dates. Phylogenetic placement of fossils demonstrates that giant body size independently evolved in multiple continental mainland taxa and confirms recent results deduced from living taxa—giantism in Testudinidae is not linked to the insular effect. An unexpected outcome is the recovery of miniaturization in Testudona (&lt;30 cm carapace length) that emerged sometime between the Oligocene and Early Miocene. No clear correlation between body size evolution and climate is apparent, but increased taxon sampling may nevertheless demonstrate the role of cooling and warming as one of many influential variables.