bluuebunny/crossref_metadata_2025 huggingface dataset:
In situ spectroelectrochemical ellipsometry using super continuum white laser: Study of the anodization of magnesium alloy
Authors: Zimmer Alexandre , Veys-Renaux Delphine , Broch Laurent , Stein Nicolas , Rocca Emmanuel
Published: October 2019

This work shows the interest to use a real time, white laser-based ellipsometer to characterize a complex electrolyte|electrode interface during an electrochemical process in an aqueous-based medium. This method is proposed to probe electrochemical interfaces that are usually not suitable to the full extent application of ellipsometry due to great disturbance of the reflected light flux provoked by gas evolution or roughness. In situ spectroelectrochemical ellipsometry combining such a visible super continuum fiber laser-band source was not previously reported to the best of the authors’ knowledge. The setup was employed to monitor an electrochemical process whose mechanism was previously incompletely described: the prespark anodization regime of the plasma electrolytic oxidation process of the Mg alloy AZ91D in the 3M KOH electrolyte. Above the anodization voltage of 4 V, the side water oxidation reaction induced light diffusion that reduces reflected light beam intensity. The process is monitored in an extended voltage range from 4 to 40 V and in an extended spectral range (495–800 nm). In the presented case, the use of a visible super continuum fiber laser-band source enhanced the signal-to-noise ratio giving access to a deeper picture of the triplex layer structure during surface repassivation by monitoring the evolution of the outer, inner, and interfacial layers.
Characterization of sound scattering using near-field pressure and particle velocity measurements
Authors: Richard Antoine , Fernández Comesaña Daniel , Brunskog Jonas , Jeong Cheol-Ho , Fernandez-Grande Efren
Published: October 2019

The acoustic properties of surfaces are commonly evaluated using samples of finite size, which generate edge diffraction effects that are often disregarded. This study makes use of sound scattering theory to characterize such finite samples. In a given sound field, the samples can be described by a unique complex directivity function called the far-field pattern. Numerical results show that the far-field pattern contains extensive information on the tested samples, including sound absorption and surface scattering, as well as scattering due to finiteness. In this paper, a method is introduced to estimate the far-field pattern of a finite sample. The method relies on measurements of the sound pressure and acoustic particle velocity in the near-field of the sample, and it makes use of the Helmholtz integral equation. The proposed technique is examined in an anechoic room where the sound field near the test sample is scanned with a three-dimensional sound intensity probe. The estimated far-field pattern is compared with numerical predictions up to 1 kHz.
Antibiotics and Host-Tailored Probiotics Similarly Modulate Effects on the Developing Avian Microbiome, Mycobiome, and Host Gene Expression
Authors: Ward Tonya L. , Weber Bonnie P. , Mendoza Kristelle M. , Danzeisen Jessica L. , Llop Katharine , Lang Kevin , Clayton Jonathan B. , Grace Elicia , Brannon Jeanine , Radovic Igor , Beauclaire Mai , Heisel Timothy J. , Knights Dan , Cardona Carol , Kogut Mike , Johnson Casey , Noll Sally L. , Arsenault Ryan , Reed Kent M. , Johnson Timothy J.
Published: October 2019

Alternative approaches are greatly needed to reduce the need for antibiotic use in food animal production. This study utilized a pipeline for the development of a host-tailored probiotic to enhance performance in commercial turkeys and modulate their microbiota, similar to the effects of low-dose antibiotic administration. We determined that a host-tailored probiotic, developed in the context of the commercial turkey gut microbiome, was more effective at modulating these parameters than a nontailored probiotic cocktail. Furthermore, the host-tailored probiotic mimicked many of the effects of a low-dose antibiotic growth promoter. Surprisingly, the effects of the antibiotic growth promoter and host-tailored probiotic were observed across kingdoms, illustrating the coordinated interkingdom effects of these approaches. This work suggests that tailored approaches to probiotic development hold promise for modulating the avian host and its microbiota.
Probiotic Yeasts Inhibit Virulence of Non
-albicans Candida
Species
Authors: Kunyeit Lohith , Kurrey Nawneet K. , Anu-Appaiah K. A. , Rao Reeta P.
Published: October 2019

Non-
albicans Candida
-associated infections have emerged as a major risk factor in the hospitalized and immunecompromised patients. Besides, antifungal-associated complications occur more frequently with these non-
albicans Candida
species than with
C. albicans
. Therefore, as an alternative approach to combat these widespread non-
albicans Candida
-associated infections, here we showed the probiotic effect of two yeasts,
Saccharomyces cerevisiae
(strain KTP) and
Issatchenkia occidentalis
(ApC), in preventing adhesion and biofilm formation of five non-
albicans Candida
strains,
Candida tropicalis
,
Candida krusei
,
Candida glabrata
,
Candida parapsilosis
, and
Candida auris
. The result would influence the current trend of the conversion of conventional antimicrobial therapy into beneficial probiotic microbe-associated antimicrobial treatment.
Retinoblastoma in an adult: a diagnostic dilemma
Authors: Mukhija Ritika , Lomi Neiwete , Kumar Saumya , Sen Seema
Published: October 2019

We report a case of a man aged 35 years who presented with the chief complaint of painless diminution of vision in the right eye for 4 months. Examination revealed a large inferior retinochoroidal mass along with retinal detachment. An anterior choroidal mass with moderate internal reflectivity was seen on B-scan ocular ultrasonography and MRI and CT scan were indicative of a mitotic aetiology. Fluorodeoxyglucose-positron emission tomography scan ruled out any other systemic foci of involvement. Based on the above findings, a provisional diagnosis of amelanotic choroidal melanoma was made and he was taken up for choroidal aspiration biopsy, wherein the cytopathology report revealed hypercellularity with no identifiable pigments. In view of the above, a diagnosticandtherapeutic enucleation was performed; however, the histopathology report of the enucleated specimen revealed poorly differentiated retinoblastoma. This case highlights that the diagnosis of retinoblastoma should be kept in mind even in adult patients.
Concomitant presentation of IgG4-negative idiopathic retroperitoneal fibrosis and Addison’s disease
Authors: Riley Mark , Saad Shaukat Muhammad Hamza , Bari Mohammed , Peredo-Wende Ruben
Published: October 2019

We describe a patient who was admitted to our medical centre with acute renal failure, hyponatraemia and hyperkalaemia. CT of the abdomen and pelvis showed a retroperitoneal mass with bilateral ureteral obstruction. Biopsy revealed fibrosis with inflammatory infiltrate, but rare IgG4-positive plasma cells. After placement of bilateral pigtail nephrostomy catheters, renal failure improved but metabolic derangements remained. Morning serum cortisol level was equivocal, but with blunted response on cosyntropin stimulation testing indicating adrenal insufficiency. Serology for 21-hydroxylase antibodies was strongly positive, supporting the diagnosis of Addison’s disease. In addition to nephrostomy catheters for obstructive uropathy, idiopathic retroperitoneal fibrosis was treated with mycophenolate mofetil. Physiological doses of hydrocortisone and fludrocortisone for Addison’s disease were also initiated. The patient continues to be monitored for regression of the mass. Based on review of the literature, this is the first reported case of IgG4-negative idiopathic retroperitoneal fibrosis presenting with autoimmune primary adrenal insufficiency.
Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis: updated definitions, scoring rules and inter-reader reliability in a multiple reader setting
Authors: Krabbe Simon , Østergaard Mikkel , Pedersen Susanne J , Weber Ulrich , Kröber Georg , Makysmowych Walter , Lambert Robert G W
Published: October 2019

Objective

To validate the Canada-Denmark (CANDEN) MRI scoring system for the spine in axial spondyloarthritis with updated lesion definitions.

Methods

Lesion definitions in the CANDEN system were updated and illustrated by a consensus set of reference images. Sagittal spine MRIs of 40 patients with axial spondyloarthritis obtained at baseline and at week 52 after initiation of treatment with the tumour necrosis factor inhibitor golimumab were evaluated in unknown chronology by seven readers blinded to all other data.

Results

CANDEN MRI spine inflammation score had very good reliability for status scores (single-measure intraclass correlation coefficient (ICC) of 21 reader pairs median of 0.91 (IQR 0.88–0.92)) and change scores (ICC 0.88 (0.86–0.92)). CANDEN MRI spine fat score had good to very good reliability for status scores (ICC 0.79 (0.75–0.86)) and moderate to good reliability for detecting change (ICC 0.59 (0.46–0.73)). CANDEN MRI spine bone erosion score and CANDEN MRI spine new bone formation score had slight to moderate reliability for status scores (ICC 0.38 (0.32–0.52) and 0.39 (0.27–0.49), respectively).

Conclusion

The CANDEN MRI spine scoring system allows a comprehensive evaluation of inflammation, fat, bone erosion and new bone formation of the spine in patients with axial spondyloarthritis. It demonstrated very good reliability for detecting change in inflammation, moderate to good reliability for detecting change in fat, and slight to moderate reliability for detecting bone erosions and new bone formation. Studies with longer follow-up or patients with more advanced spinal involvement may be needed to reliably detect change in bone erosion and new bone formation scores.

Trial registration number

NCT02011386.
Adiposity and asthma in adults: a bidirectional Mendelian randomisation analysis of The HUNT Study
Authors: Sun Yi-Qian , Brumpton Ben Michael , Langhammer Arnulf , Chen Yue , Kvaløy Kirsti , Mai Xiao-Mei
Published: October 2019

Background

We aimed to investigate the potential causal associations of adiposity with asthma overall, asthma by atopic status or by levels of symptom control in a large adult population and stratified by sex. We also investigated the potential for reverse causation between asthma and risk of adiposity.

Methods

We performed a bidirectional one-sample Mendelian randomisation (MR) study using the Norwegian Nord-Trøndelag Health Study population including 56 105 adults. 73 and 47 genetic variants were included as instrumental variables for body mass index (BMI) and waist-to-hip ratio (WHR), respectively. Asthma was defined as ever asthma, doctor-diagnosed asthma and doctor-diagnosed active asthma, and was further classified by atopic status or levels of symptom control. Causal OR was calculated with the Wald method.

Results

The ORs per 1 SD (4.1 kg/m2) increase in genetically determined BMI were ranged from 1.36 to 1.49 for the three asthma definitions and similar for women and men. The corresponding ORs for non-atopic asthma (range 1.42–1.72) appeared stronger than those for the atopic asthma (range 1.18–1.26), but they were similar for controlled versus partly controlled doctor-diagnosed active asthma (1.43 vs 1.44). There was no clear association between genetically predicted WHR and asthma risk or between genetically predicted asthma and the adiposity markers.

Conclusions

Our MR study provided evidence of a causal association of BMI with asthma in adults, particularly with non-atopic asthma. There was no clear evidence of a causal link between WHR and asthma or of reverse causation.
Mass-split dependence of pre-scission neutron multiplicity by four-dimensional Langevin dynamics in 16,18O, 40Ar and 64Ni-induced fusion–fission reactions
Authors: Naderi D. , Alavi S. A. , Dehghani V.
Published: October 2019

By using the multidimensional Langevin model, including elongation, neck thickness, asymmetry parameter and orientation degree of freedom, the fission dynamics of some [Formula: see text]O-, [Formula: see text]Ar- and [Formula: see text]Ni-induced fusion–fission reactions were investigated. We calculated mean pre-scission neutron kinetic energy, pre-scission neutron multiplicity and fission time. Mass-split dependence of pre-scission neutron multiplicity and sensitivity of multiplicity on different value of the level density parameter for fission and neutron emission of highly excited compound nuclei were studied. One can conclude reasonable agreement between theory and tentative results for different reactions.
Symmetry properties of complex contact space form
Authors: Belkhelfa Mohamed , Kadi Fatima Zohra
Published: October 2019

It is well known that a Sasakian space form is pseudo-symmetric [M. Belkhelfa, R. Deszcz and L. Verstraelen, Symmetry properties of Sasakian space-forms, Soochow J. Math. 31(4) (2005) 611–616], therefore it is Ricci-pseudo-symmetric. In this paper, we proved that a normal complex contact manifold is Ricci-semi-symmetric if and only if it is an Einstein manifold; moreover, we showed that a complex contact space form [Formula: see text] with constant [Formula: see text]-sectional curvature [Formula: see text] is properly Ricci-pseudo-symmetric [Formula: see text] if and only if [Formula: see text]; in this case [Formula: see text]. We gave an example of properly Ricci-pseudo-symmetric complex contact space form. On the other hand, we proved the non-existence of proper pseudo-symmetric ([Formula: see text]) complex contact space form [Formula: see text]
Low-Frequency Acoustic Propagation Through Crossing Internal Waves in Shallow Water
Authors: Shmelev Alexey , Lin Ying-Tsong , Lynch James
Published: October 2019

Crossing internal wave trains are commonly observed in continental shelf shallow water. In this paper, we study the effects of crossing internal wave structures on three-dimensional acoustic ducts with both theoretical and numerical approaches. We show that, depending on the crossing angle, acoustic energy, which is trapped laterally between internal waves of one train, can be either scattered, cross-ducted or reflected by the internal waves in the crossing train. We describe the governing physics of these effects and illustrate them for selected internal wave scenarios using full-field numerical simulations.
Magnetic Methods in Robotics
Authors: Abbott Jake J. , Diller Eric , Petruska Andrew J.
Published: October 2019

The goal of this article is to provide a thorough introduction to the state of the art in magnetic methods for remote-manipulation and wireless-actuation tasks in robotics. The article synthesizes prior works using a unified notation, enabling straightforward application in robotics. It begins with a discussion of the magnetic fields generated by magnetic materials and electromagnets, how magnetic materials become magnetized in an applied field, and the forces and torques generated on magnetic objects. It then describes systems used to generate and control applied magnetic fields, including both electromagnetic and permanent-magnet systems. Finally, it surveys work from a variety of robotic application areas in which researchers have utilized magnetic methods, including microrobotics, medical robotics, haptics, and aerospace.
Individual Differences in First Language Acquisition
Authors: Kidd Evan , Donnelly Seamus
Published: October 2019

Humans vary in almost every dimension imaginable, and language is no exception. In this article, we review the past research that has focused on individual differences (IDs) in first language acquisition. We first consider how different theoretical traditions in language acquisition treat IDs, and we argue that a focus on IDs is important given its potential to reveal the developmental dynamics and architectural constraints of the linguistic system. We then review IDs research that has examined variation in children's linguistic input, early speech perception, and vocabulary and grammatical development. In each case, we observe systematic and meaningful variation, such that variation in one domain (e.g., early auditory and speech processing) has meaningful developmental consequences for development in higher-order domains (e.g., vocabulary). The research suggests a high degree of integration across the linguistic system, in which development across multiple linguistic domains is tightly coupled.
Soluble guanylate cyclase stimulator praliciguat attenuates inflammation, fibrosis, and end-organ damage in the Dahl model of cardiorenal failure
Authors: Shea Courtney M. , Price Gavrielle M. , Liu Guang , Sarno Renee , Buys Emmanuel S. , Currie Mark G. , Masferrer Jaime L.
Published: October 2019

Reduced nitric oxide (NO) and a decrease in cGMP signaling mediated by soluble guanylate cyclase (sGC) has been linked to the development of several cardiorenal diseases. Stimulation of sGC is a potential means for enhancing cGMP production in conditions of reduced NO bioavailability. The purpose of our studies was to determine the effects of praliciguat, a clinical-stage sGC stimulator, in a model of cardiorenal failure. Dahl salt-sensitive rats fed a high-salt diet to induce hypertension and organ damage were treated with the sGC stimulator praliciguat to determine its effects on hemodynamics, biomarkers of inflammation, fibrosis, tissue function, and organ damage. Praliciguat treatment reduced blood pressure, improved cardiorenal damage, and attenuated the increase in circulating markers of inflammation and fibrosis. Notably, praliciguat affected markers of renal damage at a dose that had minimal effect on blood pressure. In addition, liver fibrosis and circulating markers of tissue damage were attenuated in praliciguat-treated rats. Stimulation of the NO-sGC-cGMP pathway by praliciguat attenuated or normalized indicators of chronic inflammation, fibrosis, and tissue dysfunction in the Dahl salt-sensitive rat model. Stimulation of sGC by praliciguat may present an effective mechanism for treating diseases linked to NO deficiency, particularly those associated with cardiac and renal failure. Praliciguat is currently being evaluated in patients with diabetic nephropathy and heart failure with preserved ejection fraction.
Interactions between Sedentary and Physical Activity Patterns, Lean Mass, and Bone Density in Arab Men
Authors: Alkahtani Shaea , Aljaloud Khalid , Yakout Sobhy , Al-Daghri Nasser M.
Published: October 2019

The study examined the associations between physical activity and appendicular lean mass (ALM), fat mass, and bone mineral density (BMD) and examined the role of physical activity on these variables. The participants included 497 men (age: 32.2±10.4 years and body mass index: 28.2±5.4 kg/m2). The study was cross-sectional, and measurements included body composition measured on dual-energy X-ray absorptiometry and self-reported physical activity assessed using the International Physical Activity Questionnaire. Physical activity, including light physical activity, was associated with increased ALM (P≤0.05). Fat indicators, including waist circumference, were positively associated with ALM (P≤0.05), but not with BMD. Physical activity, including moderate-to-vigorous physical activity, was not associated with BMD, whereas ALM and handgrip strength were significantly associated with BMD (P≤0.05). Physical activity independent of exercise intensity was directly associated with ALM and indirectly associated with BMD through increased muscle mass and strength.
Throughput-Guaranteed Distributed Channel Assignment and Scheduling Algorithms with Low Complexity for Multichannel Wireless Sensor Networks
Authors: Xu Xinyan , Zhang Fan , Yang Gangqiang , Xie Liguo , Liu Qing , Li Baozhu
Published: October 2019

In wireless sensor networks, an improved throughput capacity region can be achieved by equipping multiple channels. However, such approach inevitably brings the issue of solving the coupled channel assignment and scheduling problem. This paper put forward a low-complexity distributed channel assignment and scheduling policy for multichannel wireless sensor networks with single-hop traffic flows, named LDCS, as well as its multihop multipath extension. Under the proposed algorithms, random access and backoff time techniques are introduced to keep the complexity low and independent of the number of links and channels. Through theoretical analysis and simulation experiments, it is proved that the proposed algorithms are throughput guaranteed, and in some network scenarios, the achieved capacity region can be larger than that of other comparable distributed algorithms.
HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters
Authors: Smolińska Marta , Grzanka Dariusz , Antosik Paulina , Kasperska Anna , Neska-Długosz Izabela , Jóźwicki Jakub , Klimaszewska-Wiśniewska Anna
Published: October 2019

Gastric cancer (GC) is currently recognized as one of the most common and fatal tumor worldwide. The identification of novel biomarkers in relation to clinical information as well as extending the knowledge on a multiple crosstalk between various oncogenic pathways implicated in GC carcinogenesis seems pivotal to limit the disease-associated mortality. Therefore, we assessed the expression of HER2, NF-κB, and SATB1 in a total of 104 gastric adenocarcinomas and 30 normal gastric samples and correlated the expression patterns with each other and with some clinicopathological variables. Protein expression was examined by immunohistochemistry (IHC) on tissue microarrays (TMAs), and fluorescence in situ hybridization (FISH) was employed to detect HER2 amplification. In the studied group, HER2 and SATB1 were found to be overexpressed in gastric cancer tissue in comparison to normal gastric mucosa. The expression status of the former protein was seen to differ according to some clinicopathological features, but without statistical significance, whereas the expression of the latter was not importantly associated with any of them. In turn, the NF-κB protein level was significantly related to the presence of lymph node metastasis. HER2 expression was not significantly correlated with that of other proteins, but a positive correlation was found between the expression of SATB1 and NF-κB. Further studies with a larger group of patients combined with in vitro mechanistic experiments are required to fully elucidate the role and relationship of HER2, NF-κB, and SATB1 expression in gastric cancer progression. However, to the best of our knowledge, this study is the first look at a simultaneous evaluation of these three markers in the samples of gastric cancer patients.
Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts
Authors: Hutchinson Katherine E. , Yost Susan E. , Chang Ching-Wei , Johnson Radia Marie , Carr Adrian R. , McAdam Paul R. , Halligan Daniel L. , Chang Chun-Chieh , Schmolze Daniel , Liang Jackson , Yuan Yuan
Published: October 2019

Purpose:

Emerging data suggest immune checkpoint inhibitors have reduced efficacy in heavily pretreated triple-negative breast cancers (TNBC), but underlying mechanisms are poorly understood. To better understand the phenotypic evolution of TNBCs, we studied the genomic and transcriptomic profiles of paired tumors from patients with TNBC.

Experimental Design:

We collected paired primary and metastatic TNBC specimens from 43 patients and performed targeted exome sequencing and whole-transcriptome sequencing. From these efforts, we ascertained somatic mutation profiles, tumor mutational burden (TMB), TNBC molecular subtypes, and immune-related gene expression patterns. Stromal tumor-infiltrating lymphocytes (stromal TIL), recurrence-free survival, and overall survival were also analyzed.

Results:

We observed a typical TNBC mutational landscape with minimal shifts in copy number or TMB over time. However, there were notable TNBC molecular subtype shifts, including increases in the Lehmann/Pietenpol-defined basal-like 1 (BL1, 11.4%–22.6%) and mesenchymal (M, 11.4%–22.6%) phenotypes, and a decrease in the immunomodulatory phenotype (IM, 31.4%–3.2%). The Burstein-defined basal-like immune-activated phenotype was also decreased (BLIA, 42.2%–17.2%). Among downregulated genes from metastases, we saw enrichment of immune-related Kyoto Encyclopedia of Genes and Genomes pathways and gene ontology (GO) terms, and decreased expression of immunomodulatory gene signatures (P < 0.03) and percent stromal TILs (P = 0.03). There was no clear association between stromal TILs and survival.

Conclusions:

We observed few mutational shifts, but largely consistent transcriptomic shifts in longitudinally paired TNBCs. Transcriptomic and IHC analyses revealed significantly reduced immune-activating gene expression signatures and TILs in recurrent TNBCs. These data may explain the observed lack of efficacy of immunotherapeutic agents in heavily pretreated TNBCs. Further studies are ongoing to better understand these initial observations.

See related commentary by Savas and Loi, p. 526
Poor Diet, Stress, and Inactivity Converge to Form a “Perfect Storm” That Drives Alzheimer’s Disease Pathogenesis
Authors: Pacholko Anthony G. , Wotton Caitlin A. , Bekar Lane K.
Published: October 2019

North American incidence of Alzheimer’s disease (AD) is expected to more than double over the coming generation. Although genetic factors surrounding the production and clearance of amyloid-β and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a “perfect storm” to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.
Mechanisms of the Multitasking Endothelial Protein NRG-1 as a Compensatory Factor During Chronic Heart Failure
Authors: De Keulenaer Gilles W. , Feyen Eline , Dugaucquier Lindsey , Shakeri Hadis , Shchendrygina Anastasia , Belenkov Yury N. , Brink Marijke , Vermeulen Zarha , Segers Vincent F. M.
Published: October 2019

Heart failure is a complex syndrome whose phenotypic presentation and disease progression depends on a complex network of adaptive and maladaptive responses. One of these responses is the endothelial release of NRG (neuregulin)-1—a paracrine growth factor activating ErbB2 (erythroblastic leukemia viral oncogene homolog B2), ErbB3, and ErbB4 receptor tyrosine kinases on various targets cells. NRG-1 features a multitasking profile tuning regenerative, inflammatory, fibrotic, and metabolic processes. Here, we review the activities of NRG-1 on different cell types and organs and their implication for heart failure progression and its comorbidities. Although, in general, effects of NRG-1 in heart failure are compensatory and beneficial, translation into therapies remains unaccomplished both because of the complexity of the underlying pathways and because of the challenges in the development of therapeutics (proteins, peptides, small molecules, and RNA-based therapies) for tyrosine kinase receptors. Here, we give an overview of the complexity to be faced and how it may be tackled.
Sex-Based Differences in Presentation, Treatment, and Complications Among Older Adults Hospitalized for Acute Myocardial Infarction
Authors: Nanna Michael G. , Hajduk Alexandra M. , Krumholz Harlan M. , Murphy Terrence E. , Dreyer Rachel P. , Alexander Karen P. , Geda Mary , Tsang Sui , Welty Francine K. , Safdar Basmah , Lakshminarayan Dharshan K. , Chaudhry Sarwat I. , Dodson John A.
Published: October 2019

Background:

Studies of sex-based differences in older adults with acute myocardial infarction (AMI) have yielded mixed results. We, therefore, sought to evaluate sex-based differences in presentation characteristics, treatments, functional impairments, and in-hospital complications in a large, well-characterized population of older adults (≥75 years) hospitalized with AMI.

Methods and Results:

We analyzed data from participants enrolled in SILVER-AMI (Comprehensive Evaluation of Risk Factors in Older Patients With Acute Myocardial Infarction)—a prospective observational study consisting of 3041 older patients (44% women) hospitalized for AMI. Participants were stratified by AMI subtype (ST-segment–elevation myocardial infarction [STEMI] and non-STEMI [NSTEMI]) and subsequently evaluated for sex-based differences in clinical presentation, functional impairments, management, and in-hospital complications. Among the study sample, women were slightly older than men (NSTEMI: 82.1 versus 81.3,
P
<0.001; STEMI: 82.2 versus 80.6,
P
<0.001) and had lower rates of prior coronary disease. Women in the NSTEMI subgroup presented less frequently with chest pain as their primary symptom. Age-associated functional impairments at baseline were more common in women in both AMI subgroups (cognitive impairment, NSTEMI: 20.6% versus 14.3%,
P
<0.001; STEMI: 20.6% versus 12.4%,
P
=0.001; activities of daily living disability, NSTEMI: 19.7% versus 11.4%,
P
<0.001; STEMI: 14.8% versus 6.4%,
P
<0.001; impaired functional mobility, NSTEMI: 44.5% versus 30.7%,
P
<0.001; STEMI: 39.4% versus 22.0%,
P
<0.001). Women with AMI had lower rates of obstructive coronary disease (NSTEMI:
P
<0.001; STEMI:
P
=0.02), driven by lower rates of 3-vessel or left main disease than men (STEMI: 38.8% versus 58.7%; STEMI: 24.3% versus 32.1%), and underwent revascularization less commonly (NSTEMI: 55.6% versus 63.6%,
P
<0.001; STEMI: 87.3% versus 93.3%,
P
=0.01). Rates of bleeding were higher among women with STEMI (26.2% versus 15.6%,
P
<0.001) but not NSTEMI (17.8% versus 15.7%,
P
=0.21). Women had a higher frequency of bleeding following percutaneous coronary intervention with both NSTEMI (11.0% versus 7.8%,
P
=0.04) and STEMI (22.6% versus 14.8%,
P
=0.02).

Conclusions:

Among older adults hospitalized with AMI, women had a higher prevalence of age-related functional impairments and, among the STEMI subgroup, a higher incidence of overall bleeding events, which was driven by higher rates of nonmajor bleeding events and bleeding following percutaneous coronary intervention. These differences may have important implications for in-hospital and posthospitalization needs.
Check list of the Venezuelan millipedes species
Authors: BUENO-VILLEGAS JULIÁN , SIERWALD PETRA , DE ASCENÇÃO ANTONIO A.
Published: October 2019

Here we provide a checklist of millipedes described or recorded in the literature from Venezuela. The diplopod fauna is comprised of eight orders, 18 families, 54 genera, and 157 species. The millipede orders Glomerida, Chordeumatida, Julida, Siphoniulida, and Platydesmida (known elsewhere in the Western Hemisphere) are not, as of yet, reported from the Venezuelan fauna. Two widely distributed invasive species, Asiomorpha coarctata and Oxidus gracilis, were recorded from Venezuela. All species records listed here contain comprehensive citation and synonymy lists. Numerous locality data are questionable and are discussed. For most species, the supposed deposition of the type specimens is given. However, the museum and gender information is taken mostly from the literature as the type specimen themselves were not examined. An analysis of records extracted from GBIF in 2016 and in 2018 was conducted and compared to the data captured from the published taxonomic literature. The data in this checklist are summarized online at the MilliBase website.
Review of the genus Meganola Dyar, 1898 (Lepidoptera: Nolidae, Nolinae) from Korea, with the description of a new species
Authors: CHA YEONG-BIN , OH SUNG-HWAN , BAYARSAIKHAN ULZIIJARGAL , NA SOL-MOON , LEE DONG-JUNE , KO JAE-HO , KIM HYEONG-KYU , JANG CHANG-MOON , BAE YANG-SEOP
Published: October 2019

The genus Meganola Dyar, 1898 is reviewed for Korea, with 12 species, including the new species, Meganola parki Oh & Cha, sp. n. Illustrations of adults and genitalia of all the Korean species are provided, with a key to species of Meganola based on the external morphology and male genitalia. All known host plants are provided, some of them newly recorded.
Frailty, Acute Organ Dysfunction, and Increased Disability After Hospitalization in Older Adults Who Survive Critical Illness: A Prospective Cohort Study
Authors: Hope Aluko A. , Law Jammie , Nair Rahul , Kim Mimi , Verghese Joe , Gong Michelle Ng
Published: October 2019

Purpose:

We aimed to describe the association between prehospital frailty (PHF), acute organ dysfunction (AOD), and posthospital disability (PHD) outcome in older adults admitted to the intensive care unit (ICU).

Methods:

In a prospective observational cohort study, we assessed PHF using the Clinical Frailty Scale (CFS) and assessed the level of AOD using Sequential Organ Failure Assessment (SOFA) scores on ICU day 1. We assessed Activities of Daily Living disability levels through to 6 months after discharge and used generalized estimating equations (log link and negative binomial family) to determine the independent association of PHF and AOD with PHD.

Results:

Of the 302 patients enrolled, 221 (73.1%) survived the hospitalization. Prehospital frailty was associated with PHD (adjusted incident rate ratio [aIRR] 95% confidence interval [95% CI] per unit increase in CFS 1.38 [1.15-1.67], P = .001). Total day 1 SOFA score was weakly associated with PHD, (aIRR [95% CI] 1.05 [1.00-1.10], P = .037) while day 1 SOFA neurologic score was strongly associated with PHD (aIRR [95% CI] 1.42 [1.24-1.62] per unit increase in SOFA neurologic score, P < .001), and these effects were independent of PHF and other premorbid factors.

Conclusions:

Both PHF and early acute brain dysfunction are important factors associated with increasing PHD in older adults who survive critical illness.
Incorporating mpMRI biopsy data into established pre-RP nomograms: potential impact of an increasingly common clinical scenario
Authors: Leong Joon Yau , Herrera-Caceres Jaime O. , Goldberg Hanan , Tham Elwin , Teplitsky Seth , Gomella Leonard G. , Fleshner Neil E. , Lallas Costas D. , Trabulsi Edouard J. , Chandrasekar Thenappan
Published: October 2019

Background:

We examine the practical application of multiparametric MRI (mpMRI) prostate biopsy data using established pre-RP nomograms and its potential implications on RP intraoperative decision-making. We hypothesize that current nomograms are suboptimal in predicting outcomes with mpMRI targeted biopsy (TBx) data.

Materials and methods:

Patients who underwent mpMRI-based TBx prior to RP were assessed using the MSKCC and Briganti nomograms with the following iterations: (1) Targeted (T) (targeted only), (2) Targeted and Systematic (TS) and (3) Targeted Augmented (TA) (targeted core data; assumed negative systematic cores for 12 total cores). Nomogram outcomes, lymph node involvement (LNI), extracapsular extension (ECE), organ-confined disease (OCD), seminal vesicle invasion (SVI), were compared across iterations. Clinically significant impact on management was defined as a change in LNI risk above or below 2% (Δ2) or 5% (Δ5).

Results:

A total of 217 men met inclusion criteria. Overall, the TA iteration had more conservative nomogram outcomes than the T. Moreover, TA better predicted RP pathology for all four outcomes when compared with the T. In the entire cohort, Δ2 and Δ5 were 16.6–25.8% and 20.3–39.2%, respectively. In the subset of 190 patients with targeted and systematic cores, TA was a better approximation of TS outcomes than T in 71% (MSKCC) and 82% (Briganti) of patients.

Conclusion:

In established pre-RP nomograms, mpMRI-based TBx often yield variable and discordant results when compared with systematic biopsies. Future nomograms must better incorporate mpMRI TBx core data. In the interim, augmenting TBx data may serve to bridge the gap.
Treatment Patterns and Clinical Outcomes for Central Retinal Vein Occlusion in the Antivascular Endothelial Growth Factor Era
Authors: Stallworth Jeannette Y. , Thomas Akshay S. , Constantine Ryan , Stinnett Sandra S. , Fekrat Sharon
Published: October 2019

Purpose:

This article describes treatment patterns and visual outcomes for central retinal vein occlusion (CRVO) in the antivascular endothelial growth factor (anti-VEGF) era.

Methods:

A retrospective cohort study of eyes diagnosed with CRVO between 2009 and 2016 was conducted. Treatment history and visual acuity (VA) measurements were abstracted from medical records and analyzed.

Results:

A total of 476 eyes of 476 patients (median age 67 years, median follow-up 25.4 months) were included. Optical coherence tomography was obtained in 93.9% and fluorescein angiography in 80% of cases on presentation. Mean VA at presentation and final visit was 20/60 and 20/94, respectively, for eyes with nonischemic CRVO, whereas that of ischemic cases remained worse than 20/800 at final follow-up. Intravitreal bevacizumab was the most common first treatment (42.2%). Intravitreal steroid was the first treatment in 3.6% and ultimately administered in 11.3% of eyes. In the first year, an average of 5.2 ± 3.6 and 2.2 ± 3.4 anti-VEGF injections were given in treatment-naive and nontreatment-naive eyes, respectively.

Conclusions:

In our real-world cohort, anti-VEGF injection burden and frequency are lower than in published clinical trials. Visual outcomes in both ischemic and nonischemic eyes with CRVO are poorer than expected and worse than those recorded in controlled trial settings.
The occurrence of wakefieldite, a rare earth element vanadate, in the rhyolitic Joe Lott Tuff, Utah, USA
Authors: Bagiński Bogusław , Macdonald Ray , Belkin Harvey E. , Kotowski Jakub , Jokubauskas Petras , Marciniak-Maliszewska Beata
Published: October 2019

The high-silica rhyolitic Joe Lott Tuff was erupted at 19.2 ± 0.4 Ma from the Mount Belknap caldera, SW Utah. Certain units in the tuff contain two species of wakefieldite, the Nd- and Y-dominant types. They occur in disseminated streaks and patches in association with rhodochrosite, calcite, Fe oxide, cerite-(Ce), and a Mn silicate (caryopilite?), thought to have been deposited from hydrothermal fluids. The wakefieldites contain the highest levels of As (≤15.34 wt.% As2O5) and P (≤5.7 wt.% P2O5) yet recorded in this mineral, indicating significant solid solution towards chernovite-(Y) and xenotime-(Y). Thorium levels are also unusually high (≤14.2 wt.% ThO2). The source of the hydrothermal fluid(s) is unknown but might be related to uranium mineralisation in the region, in that As, V and U are commonly associated in such deposits.
Chromatin State and Immunotherapy
Authors: Haining W. Nicholas
Published: October 2019

The functional impairment of T cell-mediated immunity within the tumor microenvironment (TME) is a defining feature of many cancers. Checkpoint blockade therapy seeks to reinvigorate T cell responses by targeting inhibitory receptors such as PD-1, which are upregulated by dysfunctional TILs. However, the fundamental mechanisms underlying T cell dysfunction in the TME remain poorly understood, as are the mechanisms by which checkpoint blockade overcomes this dysfunction. Initial studies of dysfunctional CD8+ T cells in both human and mouse tumors suggested that they share features of T cell exhaustion, including co-inhibitory receptor upregulation and defects in cytokine production. However, more recent studies have suggested that TIL dysfunction is a unique state that is distinct from T cell exhaustion. Here we show that anti-PD-1 therapy acts on a specific subpopulation of CD8+ tumor-infiltrating lymphocytes (TILs) in melanoma mouse models as well as patients with melanoma. We find that dysfunctional CD8+ TILs possess canonical epigenetic and transcriptional features of T cell exhaustion, mirroring those seen in chronic viral infection. Similar to chronic viral infection, exhausted CD8+ TILs contain a subpopulation of "stem-like exhausted" T cells that have a distinct regulatory state. Stem-like exhausted TILs also have critical functional attributes that are not shared by the majority "terminally exhausted" TILs: they retain more polyfunctionality, persist following transfer into tumor-bearing mice, and differentiate to repopulate terminally exhausted TILs in the TME. As a result, stem-like exhausted CD8+ TILs are better able to control tumor growth than terminally exhausted cells. Stem-like exhausted, but not terminally exhausted, CD8+ TILs can respond to anti-PD-1 therapy without reversion of their exhausted epigenetic state. CD8+ T cells with a stem-like exhausted phenotype can be found in human melanoma samples and patients with a higher fraction of this subpopulation in their tumors have a significantly longer duration of response to combination checkpoint blockade therapy. Responsiveness to checkpoint blockade is therefore restricted to a subpopulation of exhausted TILs that retain specific functional properties which enable them to control tumors. Approaches to expand stem-like exhausted CD8+ T cells in the tumor microenvironment may be an important component of improving checkpoint blockade response.

Disclosures

Haining: Rheos Medicines: Consultancy; Iomx Therapeutics: Consultancy; Third Rock Ventures: Consultancy; Roche: Research Funding; Calico: Research Funding; Novartis: Research Funding; Tango Therapeutics: Consultancy, Equity Ownership.
Endothelium-Derived Microparticles: Functions and Clinical Relevance
Authors: Fish Jason
Published: October 2019

Extracellular vesicles (EVs) are receiving increased attention as circulating biomarkers of disease. Since they are produced by cells of the cardiovascular system, their contents (including lipids, proteins and microRNAs) can be measured to provide information about the relative health or dysfunction of the cardiovascular system. We recently demonstrated that healthy endothelium can package anti-inflammatory microRNAs into secreted EVs. The transfer of EV-encapsulated microRNAs can suppress monocyte activation through the targeting of genes encoding inflammatory signaling components in the recipient cell. The microRNA content of EVs therefore serve not only as a biomarker but can functionally contribute to cell-cell communication in the cardiovascular system to affect vascular health and disease. We have developed a methodology for high-throughput profiling of microRNAs in human plasma EV samples and will present data elucidating microRNA biomarkers in the setting of co-morbidities that elevate cardiovascular risk. In these settings, we are identifying predictive biomarkers of cardiovascular disease and are determining the functional importance of EVs to disease progression.

Disclosures

No relevant conflicts of interest to declare.
Extracellular Vesicle microRNA: A Biomarker for Vascular Dysfunction in Pregnancy?
Authors: Laurent Louise
Published: October 2019

Placental dysfunction, including preeclampsia and fetal growth restriction, is a leading contributor to maternal and fetal morbidity and mortality. Development of effective prevention and treatment strategies has been limited by lack of identification of at-risk pregnancies. We performed small RNA sequencing of maternal serum microRNAs (miRNAs) to discover and independently verify biomarkers differentially expressed in patients who later developed preeclampsia. In this study, maternal serum was collected between 17-28 weeks gestation in two cohorts: The high-risk UCSD Placenta Study (19 cases, 29 controls); and the Sera Prognostics PAPR Study (54 cases, 110 controls). Samples were divided into Discovery (2/3) and Verification sets (1/3). Cases and controls were matched for gestational age (GA) at blood draw. miRNAs were isolated and sequenced to yield miRNA counts. Individual miRNAs and pairwise ratios (reversals) were tested in blinded verification. Biomarker discovery and verification were performed on the entire GA range and for 3 GA windows: 170/7 - 215/7 (Early); 195/7 - 244/7 (Middle); and 222/7 - 280/7 (Late) weeks. In Discovery, best performing miRNAs and reversals were selected for each GA window. Performance was then confirmed in blinded Verification (Table 2). 7/50 Early GA reversals had significant AUCs (mean Discovery AUC 0.78, mean Verification AUC 0.79). 21/50 Late GA reversals had significant AUCs (mean Discovery AUC 0.71, mean Verification AUC 0.68). Of biological importance, verified reversals contained a high proportion of miRNAs that were strongly expressed in placenta and/or encoded in the chr14q32 and chr19q13 miRNA clusters. miR-155-5p, present in 21 verified reversals, has been reported to mediate repression of eNOS by TNFα, which is a regulatory interaction associated with preeclampsia. We identified and verified differentially abundant miRNAs in maternal serum at 17-28 weeks GA in pregnancies that later developed signs and symptoms of preeclampsia compared to pregnancies with uncomplicated outcomes. Our findings suggest that maternal serum miRNAs may be useful as biomarkers for prediction of placental dysfunction and warrant validation in large independent cohorts.

Disclosures

No relevant conflicts of interest to declare.
Chronic Innate Immune Signaling in Myelodysplasia
Authors: Starczynowski Daniel T.
Published: October 2019

Chronic inflammatory diseases associated with activated innate immune signaling pathways often precede Myelodysplastic Syndromes (MDS), thus a role for chronic innate immune signaling in hematopoietic cells is suspected in the development of MDS. The innate immune system recognizes pathogens and host cellular by-products by pattern recognition receptors (PRR). Among the first PRRs to be identified were the Toll-like receptors (TLRs), which consist of 10 human members. Upon binding to ligand, TLRs recruit intracellular adaptors, kinases, and effector molecules which results in pathway activation. Chronic TLR signaling impairs HSC function, creates an inflammatory environment, and alters normal hematopoiesis, which suggests a causal role in MDS. Despite growing evidence linking dysregulation of innate immune signaling in MDS, how sustained activation of innate immune signaling downstream of various receptor families contributes to MDS remains an open question. This talk will highlight the recent evidence that implicates a cell-intrinsic role of innate immune pathway activation in MDS HSC and environmental inflammatory factors that are involved in the pathogenesis of MDS.

Disclosures

No relevant conflicts of interest to declare.