bluuebunny/crossref_metadata_2025_split huggingface dataset:
OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF FLAT IRREGULAR PIGMENT EPITHELIUM DETACHMENT IN CHRONIC CENTRAL SEROUS CHORIORETINOPATHY
Authors: Bousquet Elodie , Bonnin Sophie , Mrejen Sarah , Krivosic Valérie , Tadayoni Ramin , Gaudric Alain 
Published: March 2017

Purpose:
To assess the rate of choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA) in flat irregular pigment epithelium detachment (PED) in chronic central serous chorioretinopathy.

Methods:
Data on all consecutive patients with chronic central serous chorioretinopathy who underwent OCTA over a 1-year period were reviewed. The presence of flat irregular PED, which was defined as an irregular elevation of the retinal pigment epithelium allowing the visualization of a distinct Bruch's membrane was assessed on high-resolution OCT B-scan. Clinical, multimodal imaging, and OCTA data were reviewed by two graders for the detection of CNV.

Results:
Eighty-eight eyes of 61 patients with chronic central serous chorioretinopathy were included. Patient mean age (±SD) was 54.5 ± 12.2 years, and 78.7% were males. Mean subfoveal choroidal thickness (±SD) was 452.6 ± 145.6 μm. Flat irregular PEDs were detected in 59 eyes of 51 patients. OCTA detected the presence of CNV in flat irregular PEDs in 35.6% of cases. Conversely, using the combination of spectral domain optical coherence tomography angiography, fluorescein and indocyanine green angiography, CNV was detected in only 25% of flat irregular PEDs. All hyporeflective flat irregular PEDs on OCT were avascular on OCTA while they were at least partially hyperreflective when associated with CNV.

Conclusion:
One-third of flat irregular PEDs in chronic central serous chorioretinopathy contained CNV. OCTA detected CNV more frequently than the other imaging modalities. Further longitudinal studies are needed to assess the indication of antivascular endothelial growth factor treatments in such cases.
HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy
Authors: Krukowski Karen , Ma Jiacheng , Golonzhka Olga , Laumet Geoffroy O. , Gutti Tanuja , van Duzer John H. , Mazitschek Ralph , Jarpe Matthew B. , Heijnen Cobi J. , Kavelaars Annemieke 
Published: March 2017

Abstract
Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration–approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin–dependent intracellular mitochondrial transport. Here, we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. We used a novel HDAC6 inhibitor ACY-1083, which shows 260-fold selectivity towards HDAC6 vs other HDACs. Our results show that HDAC6 inhibition prevented cisplatin-induced mechanical allodynia, and also completely reversed already existing cisplatin-induced mechanical allodynia, spontaneous pain, and numbness. These findings were confirmed using the established HDAC6 inhibitor ACY-1215 (Ricolinostat), which is currently in clinical trials for cancer treatment. Mechanistically, treatment with the HDAC6 inhibitor increased α-tubulin acetylation in the peripheral nerve. In addition, HDAC6 inhibition restored the cisplatin-induced reduction in mitochondrial bioenergetics and mitochondrial content in the tibial nerve, indicating increased mitochondrial transport. At a later time point, dorsal root ganglion mitochondrial bioenergetics also improved. HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.
Elevated procalcitonin is associated with bacterial infection during acute liver failure only when unrelated to acetaminophen intoxication
Authors: Mallet Maxime , Haq Maela , Tripon Simona , Bernard Maguy , Benosman Hedi , Thabut Dominique , Rudler Marika 
Published: March 2017

Aim
The aim of this study was to evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection and survival without transplantation upon admission in the ICU for acute liver failure (ALF).

Patients and methods
From January 2009 until October 2015, all cases of ALF patients admitted in our ICU were retrospectively reviewed and included in the study if the PCT level upon admission was available. Patients with pre-existing liver pathology or ALF in a context of already advanced multiorgan failure were excluded. The main clinical and biological characteristics of patients were recorded, as well as the etiology of ALF, diagnosis of bacterial infection (bacteriologically documented or suspected), and outcome.

Results
35 patients were included: 46% men, mean age 42 years, initial prothrombin ratio 31%, PCT 9.8 mg/l (0.7–49), and PCT more than 2 mg/l in 54% of cases. Etiology was acetaminophen intoxication in 18/35 (51%) cases. Sepsis was diagnosed in 9/35 (26%) cases, most frequently pneumonia with 4/9 cases. Survival without liver transplantation (LT) was observed in 28 (80%) cases. The median PCT was not different in patients with or without bacterial infection [6.3 mg/l (0.6–16) vs. 1.2 mg/l (0.8–9.7), P=0.8]. The median PCT was not different in patients who survived without LT [7.1 mg/l (0.9–16.1) vs. 0.75 mg/l (7.7–11.5), P=0.06]. In patients with ALF unrelated to acetaminophen intoxication, the median PCT was higher in patients with bacterial infection [1.1 mg/l (0.9–4) vs. 0.5 mg/l (0.3–0.8), P=0.01], but was similar in patients who did not survive without LT [0.7 mg/l (0.4–1.1) vs. 0.8 mg/l (0.4–2.2), P=0.6]. In the overall cohort, the median C-reactive protein (CRP) and leukocyte count were higher in patients who developed bacterial infection [40 mg/l (19–60) vs. 16 mg/l (6–34), P=0.04; 11.9 G/l (8.3–19) vs. 7.9 G/l (6–12.6), P=0.05]. The median CRP and leukocyte count were not significantly different in survivors versus nonsurvivors without LT.

Conclusion
PCT was an accurate predictor for the diagnosis of bacterial infection only in patients with ALF unrelated to acetaminophen intoxication. CRP was higher in patients who developed infection and could also be an interesting tool in ALF patients.
Attempt to Determine the Prevalence of Two Inborn Errors of Primary Bile Acid Synthesis
Authors: Jahnel Jörg , Zöhrer Evelyn , Fischler Björn , D'Antiga Lorenzo , Debray Dominique , Dezsofi Antal , Haas Dorothea , Hadzic Nedim , Jacquemin Emmanuel , Lamireau Thierry , Maggiore Giuseppe , McKiernan Pat J. , Calvo Pier L. , Verkade Henkjan J. , Hierro Loreto , McLin Valerie , Baumann Ulrich , Gonzales Emmanuel 
Published: March 2017

ABSTRACTObjective:Inborn errors of primary bile acid (BA) synthesis are genetic cholestatic disorders leading to accumulation of atypical BA with deficiency of normal BA. Unless treated with primary BA, chronic liver disease usually progresses to cirrhosis and liver failure before adulthood. We sought to determine the prevalence of 2 common disorders, 3β‐hydroxy‐Δ5‐C27‐steroid dehydrogenase (3β‐HSD) and Δ4–3‐oxosteroid‐5β‐reductase (Δ4–3‐oxoR) deficiencies and to describe current diagnostic and treatment strategies among different European paediatric hepatology centres.Methods:A total of 52 clinical paediatric centres were approached and 39 centres in 21 countries agreed to participate in the Web‐based survey. The survey comprised questions regarding general information, number of cases, diagnostic, and therapeutic management.Results:Seventeen centres located in 11 countries reported patients with inborn errors in primary BA synthesis, 22 centres never had cases diagnosed. In total, we could identify 63 patients; 55 with 3β‐HSD and 8 with Δ4–3‐oxoR deficiency in 21 countries. The minimum estimated combined prevalence of these diseases was 1.13 cases per 10 million (0.99 and 0.14 for 3β‐HSD and Δ4–3‐oxoR deficiencies, respectively). The surveyed colleagues indicated their main challenges to be the rarity of diseases and the lack of convenient laboratory facilities nearby.Conclusion:We have identified the largest cohort of patients with 3β‐HSD or Δ4–3‐oxoR deficiency described so far. These diseases are likely underdiagnosed mainly due to unawareness of their existence and the lack of laboratory facilities.
Novel Mutations in SH2D1A Gene in X-linked Lymphoproliferative Syndrome, Diagnosed After B-Cell Non-Hodgkin Lymphoma
Authors: Sharapova Svetlana O. , Fedorova Alina S. , Pashchenko Olga E. , Vahliarskaya Svetlana S. , Guryanova Irina E. , Migas Alexandr A. , Kondratenko Irina V. , Aleinikova Olga V. 
Published: March 2017

Background:
X-linked lymphoproliferative disease type I (XLP I) is caused by mutations in the SH2D1A gene and characterized mainly by hypogammaglobulinemia and abnormal response to Epstein-Barr virus with a high predisposition to B-cell non-Hodgkin lymphoma development.

Observations:
In this article, we describe the experience of 2 centers in Belarus and in Russia that follow 3 male patients who were diagnosed with XLP I after lymphoma development and treatment. Three novel mutations c.51G>C (p.E17D), c.192G>T (p.W64C), and c.53insA (p.K18KfsX67) were found in 3 males patients with XLP I. Two of them did not have any signs of immunodeficiency before B-cell non-Hodgkin lymphoma development.

Conclusions:
We propose SH2D1A mutational screening be considered in male patients with or without hypogammaglobulinemia who received rituximab treatment for lymphoma and did not recover immunoglobulin G in a year after B-depleting therapy.
Towards reduced order modelling for predicting the dynamics of coherent vorticity structures within wind turbine wakes
Authors: Debnath M. , Santoni C. , Leonardi S. , Iungo G. V. 
Published: March 2017

The dynamics of the velocity field resulting from the interaction between the atmospheric boundary layer and a wind turbine array can affect significantly the performance of a wind power plant and the durability of wind turbines. In this work, dynamics in wind turbine wakes and instabilities of helicoidal tip vortices are detected and characterized through modal decomposition techniques. The dataset under examination consists of snapshots of the velocity field obtained from large-eddy simulations (LES) of an isolated wind turbine, for which aerodynamic forcing exerted by the turbine blades on the atmospheric boundary layer is mimicked through the actuator line model. Particular attention is paid to the interaction between the downstream evolution of the helicoidal tip vortices and the alternate vortex shedding from the turbine tower. The LES dataset is interrogated through different modal decomposition techniques, such as proper orthogonal decomposition and dynamic mode decomposition. The dominant wake dynamics are selected for the formulation of a reduced order model, which consists in a linear time-marching algorithm where temporal evolution of flow dynamics is obtained from the previous temporal realization multiplied by a time-invariant operator.
This article is part of the themed issue ‘Wind energy in complex terrains’.
A Statistical Model of Shared Variability in the Songbird Auditory System
Authors: Buesing Lars , Calabrese Ana , Cunningham John P. , Woolley Sarah M. N. , Paninski Liam 
Published: March 2017

AbstractVocal communication evokes robust responses in primary auditory cortex (A1) of songbirds, and single neurons from superficial and deep regions of A1 have been shown to respond selectively to songs over complex, synthetic sounds. However, little is known about how this song selectivity arises and manifests itself on the level of networks of neurons in songbird A1. Here, we examined the network-level coding of song and synthetic sounds in A1 by simultaneously recording the responses of multiple neurons in unanesthetized zebra finches. We developed a latent factor model of the joint simultaneous activity of these neural populations, and found that the shared variability in the activity has a surprisingly simple structure; it is dominated by an unobserved latent source with one degree-of-freedom. This simple model captures the structure of the correlated activity in these populations in both spontaneous and stimulus-driven conditions, and given both song and synthetic stimuli. The inferred latent variability is strongly suppressed under stimulation, consistent with similar observations in a range of mammalian cortical regions.
Genetic variability in the promoter region of TNF-α gene in the reservoir of Junin virus, Calomys musculinus (Rodentia, Cricetidae)
Authors: Chiappero Marina B. , Cabaña Imanol , Calderón Gladys E. , Gardenal Cristina N. 
Published: March 2017

AbstractIn this study, we assessed the genetic variability of the promoter region of TNF-α gene in three natural populations of the cricetid rodentCalomys musculinus. This species is the natural reservoir of Junin virus, the etiological agent of Argentine Hemorrhagic fever. We found different levels of variability and varying signatures of natural selection in populations with different epidemiological histories.
Microbial glycoside hydrolases as antibiofilm agents with cross-kingdom activity
Authors: Snarr Brendan D. , Baker Perrin , Bamford Natalie C. , Sato Yukiko , Liu Hong , Lehoux Melanie , Gravelat Fabrice N. , Ostapska Hanna , Baistrocchi Shane R. , Cerone Robert P. , Filler Elan E. , Parsek Matthew R. , Filler Scott G. , Howell P. Lynne , Sheppard Donald C. 
Published: March 2017

AbstractGalactosaminogalactan and Pel are cationic heteropolysaccharides produced by the opportunistic pathogens,Aspergillus fumigatusandPseudomonas aeruginosa, respectively. These exopolysaccharides both contain 1,4-linkedN-acetyl-D-galactosamine and play an important role in biofilm formation by these organisms. Proteins containing glycoside hydrolase domains have recently been identified within the biosynthetic pathway of each exopolysaccharide. Recombinant hydrolase domains from these proteins (Sph3hfromA. fumigatusand PelAhfromP. aeruginosa) were found to degrade their respective polysaccharidesin vitro. We therefore hypothesized that these glycoside hydrolases could exhibit anti-biofilm activity, and further, given the chemical similarity between galactosaminogalactan and Pel, that they might display cross-species activity. Treatment ofA. fumigatuswith Sph3hdisruptedA. fumigatusbiofilms with an EC50of 0.4 nM. PelAhtreatment also disrupted pre-formedA. fumigatusbiofilms with EC50values similar to those obtained for Sph3h. In contrast, Sph3hwas unable to disruptP. aeruginosaPel-based biofilms, despite being able to bind to the exopolysaccharide. Treatment ofA. fumigatushyphae with either Sph3hor PelAhsignificantly enhanced the activity of the antifungals posaconazole, amphotericin B and caspofungin, likely through increasing antifungal penetration of hyphae. Both enzymes were non-cytotoxic and protected A549 pulmonary epithelial cells fromA. fumigatus-inducedcell damage for up to 24 hours. Intratracheal administration of Sph3hwas well tolerated, and reduced pulmonary fungal burden in a neutropenic mouse model of invasive aspergillosis. These findings suggest that glycoside hydrolases can exhibit activity against diverse microorganisms and may be useful as therapeutic agents by degrading biofilms and attenuating virulence.SignificanceThe production of biofilms is an important strategy used by both bacteria and fungi to colonize surfaces and to enhance resistance to killing by immune cells and antimicrobial agents. We demonstrate that glycoside hydrolases derived from the opportunistic fungusAspergillus fumigatusand Gram-negative bacteriumPseudomonas aeruginosacan be exploited to disrupt pre-formed fungal biofilms and reduce virulence. Additionally, these glycoside hydrolases can be utilized to potentiate antifungal drugs by increasing their hyphal penetration, to protect human cells from fungal-induced injury and to attenuate virulence ofA. fumigatusin a mouse model of invasive aspergillosis. The findings of this study identify recombinant microbial glycoside hydrolases as promising therapeutics with the potential for anti-biofilm activity against pathogens across different taxonomic kingdoms.
Biases in multivariate neural population codes
Authors: Keemink Sander W. , van Rossum Mark C. W. 
Published: March 2017

AbstractThroughout the nervous system information is typically coded in activity distributed over large population of neurons with broad tuning curves. In idealized situations where a single, continuous stimulus is encoded in a homogeneous population code, the value of an encoded stimulus can be read out without bias. Here we find that when multiple stimuli are simultaneously coded in the population, biases in the estimates of the stimuli and strong correlations between estimates can emerge. Although bias produced via this novel mechanism can be reduced by competitive coding and disappears in the complete absence of noise, the bias diminishes only slowly as a function of neural noise level. A Gaussian Process framework allows for accurate calculation of the bias and shows that a bimodal estimate distribution underlies the bias. The results have implications for neural coding and behavioral experiments.
The Protein Phosphatase 4 complex promotes the Notch pathway andwinglesstranscription
Authors: Hall Eric T. , Pradhan-Sundd Tirthadipa , Samnani Faaria , Verheyen Esther M. 
Published: March 2017

AbstractThe Wnt/Wingless (Wg) pathway controls cell fate specification, tissue differentiation and organ development across organisms. Using anin vivoRNAi screen to identify novel kinase and phosphatase regulators of the Wg pathway, we identified subunits of the serine threonine phosphatase Protein phosphatase 4 (PP4). Knockdown of the catalytic and the regulatory subunits of PP4 cause reductions in the Wg pathway targets Senseless and Distal-less. We find that PP4 regulates the Wg pathway by controlling Notch-drivenwgtranscription. Genetic interaction experiments identified that PP4 likely promotes Notch signaling within the nucleus of the Notch-receiving cell. Although the PP4 complex is implicated in various cellular processes, its role in the regulation of Wg and Notch pathways was previously uncharacterized. Our study identifies a novel role of PP4 in regulating Notch pathway, resulting in aberrations in Notch-mediated transcriptional regulation of the Wingless ligand. Furthermore, we show that PP4 regulates proliferation independent of its interaction with Notch.Summary statementThe protein phosphatase 4 complex promotes Notch signaling and target gene expression during Drosophila wing development.
The fitness cost of mis-splicing is the main determinant of alternative splicing patterns
Authors: Saudemont Baptiste , Popa Alexandra , Parmley Joanna L. , Rocher Vincent , Blugeon Corinne , Necsulea Anamaria , Meyer Eric , Duret Laurent 
Published: March 2017

ABSTRACTMost eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of functional protein variants or to the regulation of gene expression, notably via nonsense-mediated mRNA decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts, and the question of the relative proportion of splicing errors vs. functional splice variants remains highly debated. We propose here a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We first analyzed the transcriptome of the intron-rich unicellular eukaryoteParamecium tetraurelia.We show that both in normal and in NMD-deficient cells, AS rates (intron retention, alternative splice site usage or cryptic intron splicing) strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed both for AS events that are detectable by NMD or not, which invalidates the hypothesis of a possible link with the regulation of gene expression. Our results indicate that in genes with a median expression level, 92%-98% of observed splice variants correspond to errors. Interestingly, we observed the same patterns in human transcriptomes. These results are consistent with the mutation-selection-drift theory, which predicts that genes under weaker selective pressure should accumulate more maladaptive substitutions, and therefore should be more prone to errors of gene expression.
Effects of Social Organization, Trap Arrangement and Density, Sampling Scale, and Population Density on Bias in Population Size Estimation Using Some Common Mark-Recapture Estimators
Authors: Gupta Manan , Joshi Amitabh , Vidya T. N. C. 
Published: March 2017

AbstractMark-recapture estimators are commonly used for population size estimation, and typically yield unbiased estimates for most solitary species with low to moderate home range sizes. However, these methods assume independence of captures among individuals, an assumption that is clearly violated in social species that show fission-fusion dynamics, such as the Asian elephant. In the specific case of Asian elephants, doubts have been raised about the accuracy of population size estimates. More importantly, the potential problem for the use of mark-recapture methods posed by social organization in general has not been systematically addressed. We developed an individual-based simulation framework to systematically examine the potential effects of type of social organization, as well as other factors such as trap density and arrangement, spatial scale of sampling, and population density, on bias in population sizes estimated by POPAN, Robust Design, and Robust Design with detection heterogeneity. In the present study, we ran simulations with biological, demographic and ecological parameters relevant to Asian elephant populations, but the simulation framework is easily extended to address questions relevant to other social species. We collected capture history data from the simulations, and used those data to test for bias in population size estimation. Social organization significantly affected bias in most analyses, but the effect sizes were variable, depending on other factors. Social organization tended to introduce large bias when trap arrangement was uniform and sampling effort was low. POPAN clearly outperformed the two Robust Design models we tested, yielding close to zero bias if traps were arranged at random in the study area, and when population density and trap density were not too low. Social organization did not have a major effect on bias for these parameter combinations at which POPAN gave more or less unbiased population size estimates. Therefore, the effect of social organization on bias in population estimation could be removed by using POPAN with specific parameter combinations, to obtain population size estimates in a social species.