bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ophthalmologic findings associated withRhodococcus equibronchopneumonia in foals
Authors: Tarancón Iciar , Leiva Marta , Jose‐Cunilleras Eduard , Ríos José , Peña Teresa 
Published: February 2019

AbstractObjectiveTo describe ocular findings associated withRhodococcus equibronchopneumonia in foals, and to determine whether severity of the ocular lesions is related with outcome.Animals studiedFoals diagnosed withR equiinfection at the VTH‐UAB from January 2002 to December 2017.ProcedureRhodococcus equiinfection was diagnosed by means of clinical signs, radiographic/ultrasonographic findings, and/or positive culture. In all the foals, a complete ophthalmic examination by a boarded ophthalmologist was performed and ocular signs were recorded and graded (0‐4).ResultsThirty‐nine foals were included in the study, from which 12 showed signs of bilateral anterior uveitis (30.8%). Among these,three foals were classified as mildly uveitis‐affected (MUA:7.7%) and nine as severely uveitis‐affected (SUA:23.1%). Five SUA foals showed green aqueous flare (5/9;55.5%).Despite the systemic treatment, 9/39 sick foals died (23.1%), the fatality rate being different between groups: SUA (4/9;44.4%), MUA (0/3; 0%) and nonuveitis‐affected foals (5/27;18.5%). Among SUA foals, only one with green aqueous flare died (1/5;20%).ConclusionBilateral anterior uveitis is highly prevalent in foals withR equipneumonia (30.8%). The severity of anterior uveitis might be considered a nonsurvival prognostic factor and, until proven otherwise, green aqueous flare could be taken as a strongly suggestive ocular sign of the disease. Findings of this study remark the clinical relevance of performing a complete ophthalmic examination in sick foals, in order to help in the diagnosis and prognosis of uveal diseases, as well as to guaranteeing visual soundness.
Optimization of a gravity‐driven membrane (GDM) system operated with simple manual cleanings for household drinking water treatment
Authors: Lee Jonghun , Yi JongChan , Jung Hyejin , Park Pyung‐Kyu , Noh Soo Hong 
Published: February 2019

AbstractManual cleaning protocols were developed for a gravity‐driven membrane (GDM) module. Such a module is a promising solution for household water treatment in low‐ and middle‐income countries. A filtration system equipped with the GDM module was tested in a batchwise manner using three different feed water solutions. Two types of manual cleaning protocols were performed to delay the permeability decrease, namely cleaning between batches and long‐term cleaning (every 15 batches). The optimized protocol for cleaning between batches consisted of 3 twisting and 10 vertical shaking movements; the optimized long‐term cleaning protocol consisted of 70 vertical shaking movements for both the middle region of the module and the module header. These cleaning protocols allowed the filtration system to produce sufficient water to meet the minimum requirements for a five person family using all three kinds of feed water solutions. The module produced water without Escherichia coli, even for the wastewater influent.
The role of PHOX2B‐derived astrocytes in chemosensory control of breathing and sleep homeostasis
Authors: Czeisler Catherine M. , Silva Talita M. , Fair Summer R. , Liu Jillian , Tupal Srinivasan , Kaya Behiye , Cowgill Aaron , Mahajan Salil , Silva Phelipe E. , Wang Yangyang , Blissett Angela R. , Göksel Mustafa , Borniger Jeremy C. , Zhang Ning , Fernandes‐Junior Silvio A. , Catacutan Fay , Alves Michele J. , Nelson Randy J. , Sundaresean Vishnu , Rekling Jens , Takakura Ana C. , Moreira Thiago S. , Otero José J. 
Published: February 2019

Key points
The embryonic PHOX2B‐progenitor domain generates neuronal and glial cells which together are involved in chemosensory control of breathing and sleep homeostasis.
Ablating PHOX2B‐derived astrocytes significantly contributes to secondary hypoxic respiratory depression as well as abnormalities in sleep homeostasis.
PHOX2B‐derived astrocyte ablation results in axonal pathologies in the retrotrapezoid nucleus.
AbstractWe identify in mice a population of ∼800 retrotrapezoid nucleus (RTN) astrocytes derived from PHOX2B‐positive, OLIG3‐negative progenitor cells, that interact with PHOX2B‐expressing RTN chemosensory neurons. PHOX2B‐derived astrocyte ablation during early life results in adult‐onset O2 chemoreflex deficiency. These animals also display changes in sleep homeostasis, including fragmented sleep and disturbances in delta power after sleep deprivation, all without observable changes in anxiety or social behaviours. Ultrastructural evaluation of the RTN demonstrates that PHOX2B‐derived astrocyte ablation results in features characteristic of degenerative neuro‐axonal dystrophy, including abnormally dilated axon terminals and increased amounts of synapses containing autophagic vacuoles/phagosomes. We conclude that PHOX2B‐derived astrocytes are necessary for maintaining a functional O2 chemosensory reflex in the adult, modulate sleep homeostasis, and are key regulators of synaptic integrity in the RTN region, which is necessary for the chemosensory control of breathing. These data also highlight how defects in embryonic development may manifest as neurodegenerative pathology in an adult.
Sympathoexcitation in response to cardiac and pulmonary afferent stimulation of TRPA1 channels is attenuated in rats with chronic heart failure
Authors: Adam Ryan J. , Xia Zhiqiu , Pravoverov Kristina , Hong Juan , Case Adam J. , Schultz Harold D. , Lisco Steven J. , Zucker Irving H. , Wang Han-Jun 
Published: February 2019

Excessive sympathoexcitation characterizes the chronic heart failure (CHF) state. An exaggerated cardiac sympathetic afferent reflex (CSAR) contributes to this sympathoexcitation. Prior studies have demonstrated that the CSAR to capsaicin [transient receptor potential (TRP) vanilloid 1 agonist] is exaggerated in CHF animal models. We recently discovered that capsaicin application to the lung visceral pleura in anesthetized, vagotomized, open-chested rats increases mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA). We named this response the pulmonary spinal afferent reflex (PSAR). Due to the similarities between TRP vanilloid 1 and TRP ankyrin 1 (TRPA1) channels as well as the excessive sympathoexcitation of CHF, we hypothesized that stimulation of the CSAR and PSAR with a specific TRPA1 agonist would result in an augmented response in CHF rats (coronary ligation model) compared with sham control rats. In response to a TRPA1 agonist, both CSAR and PSAR in sham rats resulted in biphasic changes in MAP and increases in HR and RSNA 10–12 wk postmyocardial infarction (post-MI). These effects were blunted in CHF rats. Assessment of TRPA1 expression levels in cardiopulmonary spinal afferents by immunofluorescence, quantitative RT-PCR, and Western blot analysis 10–12 wk post-MI all indicates reduced expression in CHF rats but no reduction at earlier time points. TRPA1 protein was reduced in a dorsal root ganglia cell culture model of inflammation and simulated tissue ischemia, raising the possibility that the in vivo reduction of TRPA1 expression was, in part, caused by CHF-related tissue ischemia and inflammation. These data provide evidence that reflex responses to cardiopulmonary spinal afferent TRPA1 stimulation may be attenuated in CHF rather than enhanced.NEW & NOTEWORTHY Excessive sympathoexcitation characterizes chronic heart failure (CHF). The contribution of transient receptor potential ankyrin 1 (TRPA1) channel-mediated reflexes to this sympathoexcitation is unknown. We found that application of TRPA1 agonist to the heart and lung surface resulted in increased heart rate and sympathetic output and a biphasic change in mean arterial pressure in control rats. These effects were attenuated in CHF rats, decreasing the likelihood that TRPA1 channels contribute to cardiopulmonary afferent sensitization in CHF.
Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma
Authors: Atkins Isabelle , Kinnersley Ben , Ostrom Quinn T. , Labreche Karim , Il'yasova Dora , Armstrong Georgina N. , Eckel-Passow Jeanette E. , Schoemaker Minouk J. , Nöthen Markus M. , Barnholtz-Sloan Jill S. , Swerdlow Anthony J. , Simon Matthias , Rajaraman Preetha , Chanock Stephen J. , Shildkraut Joellen , Bernstein Jonine L. , Hoffmann Per , Jöckel Karl-Heinz , Lai Rose K. , Claus Elizabeth B. , Olson Sara H. , Johansen Christoffer , Wrensch Margaret R. , Melin Beatrice , Jenkins Robert B. , Sanson Marc , Bondy Melissa L. , Houlston Richard S. 
Published: February 2019

AbstractGenome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P &lt; 5.69 × 10−6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10−6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.Significance:This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.
MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS-, and NF1-Mutant Melanomas
Authors: Maertens Ophélia , Kuzmickas Ryan , Manchester Haley E. , Emerson Chloe E. , Gavin Alessandra G. , Guild Caroline J. , Wong Terence C. , De Raedt Thomas , Bowman-Colin Christian , Hatchi Elodie , Garraway Levi A. , Flaherty Keith T. , Pathania Shailja , Elledge Stephen J. , Cichowski Karen 
Published: February 2019

Abstract

Although the majority of BRAF-mutant melanomas respond to BRAF/MEK inhibitors, these agents are not typically curative. Moreover, they are largely ineffective in NRAS- and NF1-mutant tumors. Here we report that genetic and chemical suppression of HDAC3 potently cooperates with MAPK pathway inhibitors in all three RAS pathway–driven tumors. Specifically, we show that entinostat dramatically enhances tumor regression when combined with BRAF/MEK inhibitors, in both models that are sensitive or relatively resistant to these agents. Interestingly, MGMT expression predicts responsiveness and marks tumors with latent defects in DNA repair. BRAF/MEK inhibitors enhance these defects by suppressing homologous recombination genes, inducing a BRCA-like state; however, addition of entinostat triggers the concomitant suppression of nonhomologous end-joining genes, resulting in a chemical synthetic lethality caused by excessive DNA damage. Together, these studies identify melanomas with latent DNA repair defects, describe a promising drug combination that capitalizes on these defects, and reveal a tractable therapeutic biomarker.

Significance:
BRAF/MEK inhibitors are not typically curative in BRAF-mutant melanomas and are ineffective in NRAS- and NF1-mutant tumors. We show that HDAC inhibitors dramatically enhance the efficacy of BRAF/MEK inhibitors in sensitive and insensitive RAS pathway–driven melanomas by coordinately suppressing two DNA repair pathways, and identify a clinical biomarker that predicts responsiveness.
See related commentary by Lombard et al., p. 469.
This article is highlighted in the In This Issue feature, p. 453
Novel Method for Assessment of His Bundle Pacing Morphology Using Near Field and Far Field Device Electrograms
Authors: Saini Aditya , Serafini Nicholas J. , Campbell Shawn , Waugh William B. , Zimberg Ryan , Sheldon Todd J. , Kron Jordana , Kalahasty Gautham , Padala Santosh K. , Trohman Richard , Shepard Richard K. , Koneru Jayanthi N. , Vijayaraman Pugazhendhi , Ellenbogen Kenneth A. , Sharma Parikshit S. 
Published: February 2019

Background:
The 12-lead ECG is considered the gold standard to differentiate between selective (S), nonselective (NS) His bundle pacing (HBP), and right ventricular septal capture in routine clinical practice. We sought to assess the utility of device EGM recordings as a tool to identify the type of HBP morphology.

Methods:

One hundred forty-eight consecutive patients underwent HBP with a 3830 Select Secure lead (Medtronic, Inc) at 3 centers between October 2016 and October 2017. The near field V-EGM morphology (NF EGM), near field V-EGM time to peak (NF
Time to peak
), and far-field EGM QRS duration (QRSd) were recorded while pacing the His lead with simultaneous 12-lead ECG rhythm strips.

Results:

Indications for HBP were sinus node dysfunction, atrioventricular conduction disease, and cardiac resynchronization therapy in 68 (46%), 56 (38%), and 24 (16%) patients, respectively. Baseline QRSd was 108±38 ms with QRSd >120 ms in 57 (39%) patients (27 right bundle branch block, 18 left bundle branch block, and 12 intraventricular conduction delay). S-HBP was noted in 54 (36%) patients. A positive NF
EGM
and NF
Time to peak
>40 ms were highly sensitive (94% and 93%, respectively) and specific (90% and 94%) for S-HBP irrespective of baseline QRSd. All 3 parameters (+NF
EGM
, NF
Time to peak
>40 ms, and far-field EGM QRSd <120 ms) had high negative predictive value (97%, 95%, and 92%). A novel device-based algorithm for S-HBP was proposed. EGM transitions correlated with ECG transitions during threshold testing and can help accurately differentiate between S-HBP, NS-HBP, and right ventricular septal pacing with a cumulative positive predictive value of 91% (positive predictive value =100% in patients with baseline QRSd <120 ms).

Conclusions:
We propose a novel and simple criteria for accurate differentiation between S-HBP, NS-HBP, and right ventricular septal capture morphologies by careful analysis of device EGMs alone. This study paves the way for future studies to assess autocapture algorithms for devices with HBP.
Programmed His Bundle Pacing
Authors: Jastrzębski Marek , Moskal Paweł , Bednarek Agnieszka , Kiełbasa Grzegorz , Vijayaraman Pugazhendhi , Czarnecka Danuta 
Published: February 2019

Background:
During permanent nonselective His bundle (ns-HB) pacing, it is crucial to confirm HB capture/exclude that only right ventricle (RV) myocardial septal pacing is present. Because the effective refractory period (ERP) of the working myocardium is different than the ERP of the HB, we hypothesized that it should be possible to differentiate ns-HB capture from RV myocardial capture using programmed extrastimulus technique.

Methods:
In consecutive patients during HB pacemaker implantation, programmed HB pacing was delivered from the screwed-in HB pacing lead. Premature beats were introduced at 10-ms steps during intrinsic rhythm and also after a drive train of 600 ms. The longest coupling interval that resulted in an abrupt change of QRS morphology was considered equal to ERP of HB or RV myocardium.

Results:

Programmed HB pacing was performed from 50 different sites in 32 patients. In 34 of 36 cases of ns-HB pacing, the RV myocardial ERP was shorter than HB ERP (271.8±38 versus 353.0±30 ms;
P
<0.0001). Programmed HB pacing using a drive train resulted in a typical abrupt change of paced QRS morphology: from ns-HB to RV myocardial QRS (34 of 36 cases) or to selective HB QRS (2 of 36 cases). Programmed HB pacing delivered during native conduction resulted in obtaining selective HB QRS in 20 of 34 and RV myocardial QRS in 14 of 34 of the ns-HB cases. In RV myocardial–only pacing cases (false ns-HB pacing, n=14), such responses were not observed—the QRS morphology remained stable. Therefore, the programmed HB pacing correctly diagnosed all ns-HB cases and all RV myocardial pacing cases.

Conclusions:
A novel maneuver for the diagnosis of HB capture, based on the differences in ERP between HB and myocardium, was formulated, assessed, and found as diagnostically valuable. This method is unique in enabling to visualize selective HB QRS in patients with otherwise obligatory ns-HB pacing (RV myocardial capture threshold <HB capture threshold).
Simplified Echocardiography Screening Criteria for Diagnosing and Predicting Progression of Latent Rheumatic Heart Disease
Authors: Nunes Maria Carmo P. , Sable Craig , Nascimento Bruno R. , Lima Emilly Malveira de , da Silva Jose Luiz Padilha , Diamantino Adriana C. , Oliveira Kaciane K.B. , Okello Emmy , Aliku Twalib , Lwabi Peter , Colosimo Enrico Antonio , Ribeiro Antonio Luiz P. , Beaton Andrea Z. 
Published: February 2019

Background:
The 2012 World Heart Federation Criteria are the current gold standard for the diagnosis of latent rheumatic heart disease (RHD). Because data and experience using these criteria have grown, there is opportunity to simplify and develop outcome prediction tools. We aimed to develop a simple echocardiographic score applicable for RHD screening with potential to predict disease progression.

Methods:
This study included 3 cohorts used for score derivation (n=9501), score validation (n=7312), and assessment of outcomes prediction (n=227). In the derivation cohort, variables independently associated with definite RHD were assigned point values proportional to their regression coefficients. The sum of these values was stratified into low (0–6), intermediate (7–9), and high (≥10) risk.

Results:

Five components were selected for score development, including mitral valve anterior leaflet thickening, excessive leaflet tip motion, and regurgitation jet length ≥2 cm, and aortic valve focal thickening and any regurgitation. The score showed optimal discrimination and calibration for RHD diagnosis in the derivation and validation cohorts (C statistic, 0.998 and 0.994, respectively), with good discrimination for predicting disease progression (C statistic, 0.811). Progression-free survival rate in the low-risk children at 1-, 2-, and 3-year follow-up was 100%, 100%, and 93%, respectively, compared with 90%, 60%, and 47% in high-risk group. The point-based score was strongly associated with disease progression (hazard ratio, 1.270; 95% CI, 1.188–1.358;
P
<0.001).

Conclusions:
This simplified score, based on components of the World Heart Federation criteria, is highly accurate to recognize definite RHD and provides the first tool for risk stratification, assigning children with latent RHD to low, intermediate, or high risk based on echocardiographic features at diagnosis.
Observations of Thermally Driven Circulations in the Pyrenees: Comparison of Detection Methods and Impact on Atmospheric Composition Measured at a Mountaintop
Authors: Hulin M. , Gheusi F. , Lothon M. , Pont V. , Lohou F. , Ramonet M. , Delmotte M. , Derrien S. , Athier G. , Meyerfeld Y. , Bezombes Y. , Augustin P. , Ravetta F. 
Published: February 2019

AbstractThe atmospheric composition measured at the Pic du Midi high-altitude observatory (2875 m MSL) in the French Pyrenees is frequently affected by upward transport of boundary layer air during anabatic circulations at different scales. The Pyrenean Platform for Observation of the Atmosphere (P2OA) includes two observatories located 28 km apart: at the Pic du Midi and at a low-altitude site (580 m MSL) located in the plain north of the mountain chain. From a 10-yr-long data series collected at P2OA, three different methods are used to detect thermally induced circulations. The methods are based on observations collected independently at three key locations in the plain–mountain circulation cell: within the altitude return flow above the plain, close to the surface in the plain, and at the mountaintop. The main aims are 1) to present and compare the three detection methods and 2) to evaluate the impact of thermally driven circulations on in situ air composition measurements at the Pic du Midi. The first method uses radar wind measurements at 3000 and 5000 m above the plain to detect the return flow of the plain–mountain circulation. The second, which is based on surface wind data from the plain site, reveals days during which surface thermally induced winds occur locally. The third method, which is based on surface data at the mountaintop, focuses on diurnal moisture cycles to rank days with decreasing anabatic influence. We then compare the three independent detection methods, discuss possible connections among thermal circulations at different scales and locations, and present an evaluation of their impact on in situ atmospheric composition measurements at Pic du Midi.
The Winter Concurrent Meridional Shift of the East Asian Jet Streams and the Associated Thermal Conditions
Authors: Zhang Yazhou , Yan Peiwen , Liao Zhijie , Huang Danqing , Zhang Yaocun 
Published: February 2019

AbstractIn this study, the concurrent meridional shift of the East Asian polar-front jet (EAPJ) and the East Asian subtropical jet (EASJ) and the associated thermal conditions have been investigated. The concurrent meridional shift is dominantly characterized by an out-of-phase shift of the two jets, as an equatorward shift of the EAPJ and a poleward shift of the EASJ, and vice versa. This shift is linked with the dipole surface air temperature (SAT) anomaly over the Eurasian continent and a La Niña–like sea surface temperature (SST) anomaly. Associated with the dipole SAT anomaly, the meridional temperature gradient (MTG) anomaly exhibits a tripole pattern from low to high latitudes over the Eurasian continent, as well as an enhanced maximum eddy growth rate and an anomalous divergence of Eliassen–Palm flux (E-P flux) over the regions between the EAPJ and EASJ. Additionally, the synoptic-scale transient eddy activities (STEA) significantly decrease over the high latitudes and enhance between the EAPJ and EASJ. All the anomalies would benefit the equatorward and poleward shift of the EAPJ and EASJ, respectively. The MTG, E-P flux and STEA anomalies are also indicated in that associated with the Niña-like SST anomaly. Particularly, the variations are evident in low latitudes. The pathway of the stationary Rossby wave activity flux anomalies shows an eastward Rossby wave packet propagation along the southern portion of the EAPJ is associated with the SAT anomaly and that along the northern portion of the EASJ is associated with the SST anomaly. The relative contributions of the two thermal conditions have emphasized the role of the dipole SAT anomaly, based on multilinear regression.