bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing a generic synapomorphy of Pseudodebis Forster, 1964 (Lepidoptera : Nymphalidae : Satyrinae) and a recent speciation with a shift in elevation between two new species in the western Andes
Authors: Nakahara Shinichi , Matos-Maraví Pável , Schwartz Johanna , Willmott Keith R.
Published: February 2021

The field of systematics and our understanding of phylogenetic relationships have been invigorated by the use of molecular data, but analyses based on DNA sequence data are not always corroborated by diagnostic morphological characters. In particular, several taxonomic changes in butterflies (Papilionoidea) have been made solely on the basis of molecular data without identifying morphological synapomorphies that might have aided in diagnosing taxa from butterfly collections or specimens with no accessible DNA. We here focus on the butterfly genus Pseudodebis Forster, 1964 in the so-called ‘Taygetis clade’, which is one of the major clades in the diverse Neotropical nymphalid subtribe Euptychiina. We inferred the evolution of a male genitalic character using the most comprehensive molecular phylogeny for the ‘Taygetis clade’ to date. This approach allowed us to identify a synapomorphy for Pseudodebis Forster, 1964, which can be used to morphologically diagnose this genus and to distinguish it from other genera in the ‘Taygetis clade’. In addition, we describe two new species of Pseudodebis, P. nakamurai Nakahara & Willmott, sp. nov. and P. pieti Nakahara & Willmott, sp. nov., recovered as sister species based on molecular data, with an estimated time of divergence of 0.3 Ma (Bayesian confidence interval 0.03–1.61 Ma). Despite the low genetic divergence between these two Pseudodebis species, they can be readily distinguished by wing morphology. Pseudodebis nakamurai, sp. nov. and P. pieti, sp. nov. occur in partial sympatry across an elevational gradient along the western Andes, and the inferred recent speciation event might be related to a shift in elevation and possibly a change in larval hostplant preference. urn:lsid:zoobank.org:pub:38B4AF76-79E9-4D4D-BF16-FCD8F53A7277
Delivery of mRNA vaccine with a lipid-like material potentiates antitumor efficacy through Toll-like receptor 4 signaling
Authors: Zhang Hongxia , You Xinru , Wang Xiaojuan , Cui Lei , Wang Zining , Xu Feifei , Li Mengyun , Yang Zhenggang , Liu Jinyun , Huang Peng , Kang Yang , Wu Jun , Xia Xiaojun
Published: February 2021

Significance

Our study has identified a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that effectively promotes mRNA delivery and antigen presentation with a self-adjuvant feature through activating TLR4 signaling. The C1 LNP mRNA nanovaccine exhibited significant in vivo efficacy in both tumor prevention and therapeutic vaccine settings. Therefore, our work presents a mRNA nanovaccine platform for developing cancer immunotherapy for a wide range of tumor types.
Diel transcriptional oscillations of light-sensitive regulatory elements in open-ocean eukaryotic plankton communities
Authors: Coesel Sacha N. , Durham Bryndan P. , Groussman Ryan D. , Hu Sarah K. , Caron David A. , Morales Rhonda L. , Ribalet François , Armbrust E. Virginia
Published: February 2021

Significance

Most organisms coordinate key biological events to coincide with the day/night cycle. These diel oscillations are entrained through the activity of light-sensitive photoreceptors that allow organisms to respond rapidly to changes in light exposure. In the ocean, the plankton community must additionally contend with dramatic changes in the quantity and quality of light over depth. Here, we show that the predominantly blue-light field in the open-ocean environment may have driven expansion of blue light-sensitive regulatory elements in open-ocean eukaryotic plankton derived from secondary and tertiary endosymbiosis. The diel transcription of genes encoding light-sensitive elements indicate that photosynthetic and heterotrophic marine protists respond to and anticipate fluctuating light conditions in the dynamic marine environment.
β-Adrenergic control of sarcolemmal Ca
V
1.2 abundance by small GTPase Rab proteins
Authors: del Villar Silvia G. , Voelker Taylor L. , Westhoff Maartje , Reddy Gopireddy R. , Spooner Heather C. , Navedo Manuel F. , Dickson Eamonn J. , Dixon Rose E.
Published: February 2021

Significance

The L-type voltage-gated Ca
2+
channel Ca
V
1.2 is essential for excitation–contraction coupling in the heart. During the fight-or-flight response, Ca
V
1.2 channel activity is augmented as a result of PKA-mediated phosphorylation, downstream of β-adrenergic receptor activation. We discovered that enhanced sarcolemmal abundance of Ca
V
1.2 channels, driven by stimulated insertion/recycling of specific Ca
V
1.2-containing endosomes, is essential for β-adrenergic receptor-mediated regulation of these channels in the heart. These data reveal a conceptual framework of this critical and robust pathway for on-demand tuning of cardiac excitation–contraction coupling during fight-or-flight.
Functional consequences of convergently evolved microscopic skin features on snake locomotion
Authors: Rieser Jennifer M. , Li Tai-De , Tingle Jessica L. , Goldman Daniel I. , Mendelson Joseph R.
Published: February 2021

The small structures that decorate biological surfaces can significantly affect behavior, yet the diversity of animal–environment interactions essential for survival makes ascribing functions to structures challenging. Microscopic skin textures may be particularly important for snakes and other limbless locomotors, where substrate interactions are mediated solely through body contact. While previous studies have characterized ventral surface features of some snake species, the functional consequences of these textures are not fully understood. Here, we perform a comparative study, combining atomic force microscopy measurements with mathematical modeling to generate predictions that link microscopic textures to locomotor performance. We discover an evolutionary convergence in the ventral skin structures of a few sidewinding specialist vipers that inhabit sandy deserts—an isotropic texture that is distinct from the head-to-tail-oriented, micrometer-sized spikes observed on a phylogenetically broad sampling of nonsidewinding vipers and other snakes from diverse habitats and wide geographic range. A mathematical model that relates structural directionality to frictional anisotropy reveals that isotropy enhances movement during sidewinding, whereas anisotropy improves movement during slithering via lateral undulation of the body. Our results highlight how an integrated approach can provide quantitative predictions for structure–function relationships and insights into behavioral and evolutionary adaptations in biological systems.
Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity
Authors: Jayabalan Aravinth Kumar , Adivarahan Srivathsan , Koppula Aakash , Abraham Rachy , Batish Mona , Zenklusen Daniel , Griffin Diane E. , Leung Anthony K. L.
Published: February 2021

Significance

Alphaviruses are mosquito-borne RNA viruses that cause rash, arthritis, and neurologic disease. Despite a continued risk of outbreaks, there are no licensed interventions for any alphavirus. For progress in control, an understanding of the molecular targets that affect virus replication and virulence is essential. This paper characterizes a conserved macrodomain in the virulence factor nonstructural protein 3 (nsP3). We discovered that the macrodomain ADP-ribosylhydrolase activity is critical for controlling the composition of cellular condensates, specifically through regulating the localization of translation factors, during viral infection. Given that this macrodomain is conserved across alphaviruses and coronaviruses and that the associated enzymatic activity is critical for virulence, our work may open avenues for developing a class of antiviral therapeutics.
Uncovering the left periphery of Etruscan
Authors: Samo Giuseppe , Canuti Massimiliano
Published: February 2021

In this paper, we attempt to address a
Restprache like Etruscan by means of
theoretical tools. This work approaches the syntax of Etruscan and
proposes a number of descriptive generalizations on its clausal
structure. Despite the intrinsic difficulty represented by the
fragmentary data, we provide some theory-driven insights to detect
pragmatic/semantic effects based on syntax. After having presented
the theoretical insights related to word order reorderings and
syntacticization, we shall discuss qualitative data from Etruscan.
We observe that modifications of the “canonical” word order might be
related to interpretative properties. Following the criterial
approach of scope-discourse semantics, we propose that the movement
of the verb in Etruscan adjacent to the fronted XP is the strategy
to realize the activated criterial position in the left periphery.
In the last part, we also discuss attested complementizers and their
mapping within the syntactic architecture.
Subject drop in how come questions in
English
Authors: Endo Yoshio
Published: February 2021

In this paper, I will discuss a novel phenomenon
which has not previously been discussed in the literature on
how come questions – namely the fact that they
can exhibit subject drop in diary-style English. I will first
introduce Haegeman’s
(1990) analysis of diary English with special attention
to subject drop. I will next show some facts that how
come questions can exhibit subject drop in diary-style
English and suggest a mechanism responsible for subject drop in
diary English. It will be shown that the same mechanism is used to
license the null subject in Old English. I will further deal with a
related but distinct question about the mechanism licensing an
argumental element in the lower topic position in Old English, as
opposed to Late Middle English. I will finally show that the same
mechanism responsible for subject drop is used in licensing null
Case in Japanese.
Causativity alternation in the lower field
Authors: Naji Mohamed
Published: February 2021

We will argue in this paper that the lower field
of the sentence, little vP, is endowed with a new
functional category cause phrase (causP). We will severet
anticausativity from voice. We will propose that anticausative
morphology in standard Arabic (SA) is projected in syntax closer to
the root, between the root and v°. Our proposition has two important
consequences. The first one, it denies the existence of the strict
locality between a root and its categorizer. The second one, it
confirms that agentive and causer subjects will occupy different
hierarchical positions inside of the sentence (IP). We will see that
transcategorial derivations of derived nominals from the verb
conserves anticausative morphology, but it cannot do so with passive
morphology. This is a strong fact confirming the different syntactic
status of the two kinds of morphology. Moreover, the distribution of
agentive and causer subjects with subject oriented adverbs (SOA) and
manner adverbs (MA) shows an asymmetry between the two in linking
SOA and MA. We will explain this asymmetry between agent and causer
subjects by their different syntactic positions into the structure
of IP. Thereafter, we will extend our analysis to nominal events
too.
Towards a cartography of light verbs
Authors: Si Fuzhen
Published: February 2021

A common goal shared by cartographic studies is
“to draw maps as precise and detailed as possible of syntactic
configurations” (Cinque &
Rizzi 2008). In the past two decades, a great progress
has been made in the study of peripheries of different domains such
as CP domain, VP domain and DP domain. The “more precise and
detailed” cartographic research goal enables us to rethink those
projections which believed to be single projections in earlier
theoretical models. A rich literature on peripheries have shown that
many of these superficial single projections are actually
abbreviations of much richer structural zones. For instance, the C
layer is split into Topic and Focus components (Rizzi 1997; Rizzi &
Bocci 2017) and Topic and Focus themselves are also conceived as
Topic “field” and Focus “field” (Benincà & Poletto 2004), encoding different and
hierarchically arranged topic elements or focus elements. Similarly,
this chapter suggests that “light verb” can also be further analyzed
as a “light verb field”, containing several layers of different
light verbs, conveying different information. Following this
tradition, also in light of Larson (1988, 2014), Harley
(2002), and Benincà
& Poletto (2004), the present chapter provides a
zoom-in/zoom-out mental magnifier for the study of various light
verb structures. One major assumption and two subsequent assumptions
are proposed: (1) Split light verb hypothesis: from a cartographic
point of view, the light verb “v” is not “ONE”
head, but an umbrella name of a rather “rich structural” zone, call
it “light verb field” or “light verb zone”. (2) About the argument
structure, it is proposed that in the complex light verb
constructions, the core of the predicate is not composed of one
single argument structure, but a chain of several argument
structures. (3) Correspondingly, the event structure can also be
looked at in more details in these structures: the idea is that in
the sentences contain chain argument structures, the event can also
be analyzed as a chain of event fragments, following rule-to-rule
correspondence principle.
Multiple counterparts of Mandarin qu (go) in
Teochew and their cartographic distributions
Authors: Luo Zhuosi
Published: February 2021

Qu (lit. go,
去
) in Mandarin is a thorny topic for syntactic
analyses, considering that it has multiple functions but only one
phonetic form, not to mention that Mandarin also has some other
complicated syntactic constructions intertwined in the discussions.
However, in Teochew, a variety of Southern Min, which boasts a
richer phonetic and phonological system, its counterparts of
Mandarin qu have different realizations, each
corresponding to different syntactic functions. Through analyzing
these different phonetic forms in Teochew and exploring their
cartographic distributions, this paper aims to provide a new view
from the perspective of Chinese dialect on the discussions on this
topic. In addition to Zhang’s (2016: 188–197) descriptive observations on two Teochew
counterparts of Mandarin qu – k’a
and k’u, this paper also discusses another
counterpart – k’ə, analyzes their syntactic
characteristics and finds out that their cartographic distributions
are located from the VP layer all the way up to the CP layer –
namely VP, vP, AspectP, TP and SAttP in the CP domain, demonstrating
a grammaticalization process. And k’u and
k’ə are the outcome of
morphological/phonological derivation from k’u.
Some crosslinguistic comparisons between Teochew, Old Chinese,
Mandarin Chinese and English are also made to make the picture
clearer.
Jan Blommaert, linguistic landscapes and complexity
Authors: Pennycook Alastair
Published: February 2021

This tribute to the work of Jan Blommaert discusses his complex relation with the field of linguistic landscape studies. Blommaert was interested in the insights an understanding of the linguistic landscape could bring to better appreciate the ways people lived their diverse lives. This appreciation of the importance of his work focuses on his insistence on ethnographic work in order to understand complexity.
Systematic memory B cell archiving and random display shape the human splenic marginal zone throughout life
Authors: Kibler Artur , Budeus Bettina , Homp Ekaterina , Bronischewski Kevin , Berg Victoria , Sellmann Ludger , Murke Florian , Heinold Andreas , Heinemann Falko M. , Lindemann Monika , Bekeredjian-Ding Isabelle , Horn Peter A. , Kirschning Carsten J. , Küppers Ralf , Seifert Marc
Published: February 2021

Human memory B cells (MBCs) are generated and diversified in secondary lymphoid tissues throughout the organism. A paired immunoglobulin (Ig)-gene repertoire analysis of peripheral blood (PB) and splenic MBCs from infant, adult, and elderly humans revealed that throughout life, circulating MBCs are comprehensively archived in the spleen. Archive MBC clones are systematically preserved and uncoupled from class-switching. Clonality in the spleen increases steadily, but boosts at midlife, thereby outcompeting small clones. The splenic marginal zone (sMZ) represents a primed MBC compartment, generated from a stochastic exchange within the archive memory pool. This is supported by functional assays, showing that PB and splenic CD21+ MBCs acquire transient CD21high expression upon NOTCH2-stimulation. Our study provides insight that the human MBC system in PB and spleen is composed of three interwoven compartments: the dynamic relationship of circulating, archive, and its subset of primed (sMZ) memory changes with age, thereby contributing to immune aging.
A Framework for Analyzing Broadly Engaged Philosophy of Science
Authors: Plaisance Kathryn S. , Elliott Kevin C.
Published: February 2021

Philosophers of science are increasingly interested in engaging with scientific communities, policy makers, and members of the public; however, the nature of this engagement has not been systematically examined. Instead of delineating a specific kind of engaged philosophy of science, as previous accounts have done, this article draws on literature from outside the discipline to develop a framework for analyzing different forms of broadly engaged philosophy of science according to two key dimensions: social interaction and epistemic integration. Clarifying the many forms of engagement available to philosophers of science can advance future scholarship on engagement and promote more strategic engagement efforts.
Comment on ‘Pulse rate variability in cardiovascular health: a review on its applications and relationship with heart rate variability’
Authors: Hejjel László , Béres Szabolcs
Published: February 2021

Precise beat-to-beat fiducial point detection in the photoplethysmogram signal is essential for reliable pulse rate variability (PRV) analysis, which is considered an integral part of health monitoring devices in the evolving era of mobile health. Several studies have aimed to compare PRV to the well-investigated, gold standard heart rate variability (HRV) analysis, to see if they are interchangeable. The agreement between PRV and HRV is not unequivocal, as we learn from the commented metaanalysis. Technical factors like low sampling rate of photoplethysmography (PPG) or imprecise fiducial point detection are more important in this difference than physiological factors corresponding to pulse arrival time. Standardization of the PPG acquisition and reference point detection is necessary for comparable studies and correct measurement.
EMC3-EIRENE simulation of first wall recycling fluxes in W7-X with relation to H-alpha measurements
Authors: Winters V R , Reimold F , König R , Krychowiak M , Romba T , Biedermann C , Bozhenkov S , Drewelow P , Endler M , Feng Y , Frerichs H , Fuchert G , Geiger J , Gao Y , Harris J H , Jakubowski M , Kornejew P , Kremeyer T , Niemann H , Pasch E , Puig-Sitjes A , Schlisio G , Scott E R , Wurden G A
Published: February 2021

In the Wendelstein 7-X stellarator, the main locations of particle sources are expected to be the carbon divertors, baffles and graphite heat shield first wall. In this paper, the heat shield is implemented in EMC3-EIRENE to understand the expected areas and magnitudes of the recycling flux to this component. It is found that in the simulation the heat shield is not a significant source of recycling neutrals. The areas of simulated recycling flux are shown to correlate well with footprints of plasma-wetting seen in post-experimental campaign in-vessel inspection photos. EMC3-EIRENE reconstruction of line-integrated H-alpha measurements at the heat shield indicate that the majority of emission does not come from local recycling neutrals. Rather, the H-alpha signals at the heat shield are dominated by ionization of neutrals which have leaked from the divertor/baffle region into the midplane. The magnitude of the H-alpha line emission from the synthetic reconstruction is consistent with the experiment, indicating that a large overestimation of heat shield recycling would occur if these measurements were assumed to be from local recycling sources. In the future, it may be possible to obtain some information of local recycling from the heat shield since it was found that the majority of the recycling flux occurs on two well-localized areas.
Chiral switching and dynamic barrier reductions in artificial square ice
Authors: Leo Naëmi , Pancaldi Matteo , Koraltan Sabri , González Pedro Villalba , Abert Claas , Vogler Christoph , Slanovc Florian , Bruckner Florian , Heistracher Paul , Hofhuis Kevin , Menniti Matteo , Suess Dieter , Vavassori Paolo
Published: February 2021

Collective dynamics in lithographically-defined artificial spin ices offer profound insights into emergent correlations and phase transitions of geometrically-frustrated Ising spin systems. Their temporal and spatial evolution are often simulated using kinetic Monte Carlo (kMC) simulations, which rely on the precise knowledge of the switching barriers to obtain predictive results in agreement with experimental observations. In many cases, however, the barriers are derived from simplified assumptions only, and do not take into account the full physical picture of nanomagnetic switching. Here we describe how the immediate magnetic square- or kagome-ice environment of a nanomagnet reversing via quasi-coherent rotation can induce clockwise and counter-clockwise switching channels with different barrier energies. This energy splitting for chiral reversal channels can be sizeable and, as string-method micromagnetic simulations show, is relevant for artificial spin ice systems made of both exchange- as well as magnetostatically-dominated units. Due to the barrier splitting and further reductions due to non-uniform reversal, transition rates can be exponentially enhanced by several orders of magnitude compared to mean-field predictions, especially in the limit of rare switching events where thermal excitation is less likely. This leads to significantly faster relaxation time scales and modified spatial correlations. Our findings are thus of integral importance to achieve realistic kMC simulations of emergent correlations in artificial spin systems, magnonic crystals, or the evolution of nanomagnetic logic circuits.
The high-value pharmacy enterprise framework: Advancing pharmacy practice in health systems through a consensus-based, strategic approach
Authors: Rough Steve , Shane Rita , Armitstead John A , Belford Sylvia M , Brummond Philip W , Chen David , Collins Christine M , Dalton Heather , Dopp Anna Legreid , Estevez Michelle M , Hager David R , Halbach Brooke , Hays Ryan , Knoer Scott , Kotis Desi , Montgomery Derek , Plummer Brooks , Riester Melissa R , Schreier Diana J , Simonson Deborah , Siska Mark H , Waier Kelsey , Vermeulen Lee C
Published: February 2021

Purpose

The high-value pharmacy enterprise (HVPE) framework and constituent best practice consensus statements are presented, and the methods used to develop the framework’s 8 domains are described.

A panel of pharmacy leaders used an evidence- and expert opinion–based approach to define core and aspirational elements of practice that should be established within contemporary health-system pharmacy enterprises by calendar year 2025. Eight domains of an HVPE were identified: Patient Care Services; Business Services; Ambulatory and Specialty Pharmacy Services; Inpatient Operations; Safety and Quality; Pharmacy Workforce; Information Technology, Data, and Information Management; and Leadership. Phase 1 of the project consisted of the development of draft practice statements, performance elements, and supporting evidence for each domain by panelists, followed by a phase 2 in-person meeting for review and development of consensus for statements and performance elements in each domain. During phase 3, the project cochairs and panelists finalized the domain drafts and incorporated them into a full technical report and this summary report.

Conclusion

The HVPE framework is a strategic roadmap to advance pharmacy practice by ensuring safe, effective, and patient-centered medication management and business practices throughout the health-system pharmacy enterprise. Grounded in evidence and expert recommendations, the statements and associated performance elements can be used to identify strategic priorities to improve patient outcomes and add value within health systems.
The Escherichia coli CitT transporter can be used as a succinate exporter for succinate production
Authors: Takahashi Sousuke , Miyachi Mayu , Tamaki Hisanori , Suzuki Hideyuki
Published: February 2021

Escherichia coli strain, whose gene is one of the subunits of succinate dehydrogenase (sdhA), and gene of the transcriptional repressor of isocitrate lyase (iclR) were disrupted, accumulated 6.6 times as much intracellular succinate as the wild-type MG1655 strain in aerobic growth, but succinate was not found in the culture medium. E. coli citT gene that encodes a citrate transporter was cloned under the control of the lacI promoter in pBR322-based plasmid and the above strain was transformed. This transformant, grown under aerobic condition in M9-tryptone medium with citrate, accumulated succinate in the medium while no succinate was found in the medium without citrate. CitT was active as a succinate transporter for 168 h by changing the culture medium or for 24 h in fed-batch culture. This study suggests that the CitT transporter functions as a succinate exporter in E. coli for succinate production in the presence of citrate.
Imaging meningeal inflammation in CNS autoimmunity identifies a therapeutic role for BTK inhibition
Authors: Bhargava Pavan , Kim Sol , Reyes Arthur A , Grenningloh Roland , Boschert Ursula , Absinta Martina , Pardo Carlos , Van Zijl Peter , Zhang Jiangyang , Calabresi Peter A
Published: February 2021

Leptomeningeal inflammation in multiple sclerosis is associated with worse clinical outcomes and greater cortical pathology. Despite progress in identifying this process in multiple sclerosis patients using post-contrast fluid-attenuated inversion recovery imaging, early trials attempting to target meningeal inflammation have been unsuccessful. There is a lack of appropriate model systems to screen potential therapeutic agents targeting meningeal inflammation. We utilized ultra-high field (11.7 T) MRI to perform post-contrast imaging in SJL/J mice with experimental autoimmune encephalomyelitis induced via immunization with proteolipid protein peptide (PLP139–151) and complete Freund’s adjuvant. Imaging was performed in both a cross-sectional and longitudinal fashion at time points ranging from 2 to 14 weeks post-immunization. Following imaging, we euthanized animals and collected tissue for pathological evaluation, which revealed dense cellular infiltrates corresponding to areas of contrast enhancement involving the leptomeninges. These areas of meningeal inflammation contained B cells (B220+), T cells (CD3+) and myeloid cells (Mac2+). We also noted features consistent with tertiary lymphoid tissue within these areas, namely the presence of peripheral node addressin-positive structures, C-X-C motif chemokine ligand-13 (CXCL13)-producing cells and FDC-M1+ follicular dendritic cells. In the cortex adjacent to areas of meningeal inflammation we identified astrocytosis, microgliosis, demyelination and evidence of axonal stress/damage. Since areas of meningeal contrast enhancement persisted over several weeks in longitudinal experiments, we utilized this model to test the effects of a therapeutic intervention on established meningeal inflammation. We randomized mice with evidence of meningeal contrast enhancement on MRI scans performed at 6 weeks post-immunization, to treatment with either vehicle or evobrutinib [a Bruton tyrosine kinase (BTK) inhibitor] for a period of 4 weeks. These mice underwent serial imaging; we examined the effect of treatment on the areas of meningeal contrast enhancement and noted a significant reduction in the evobrutinib group compared to vehicle (30% reduction versus 5% increase; P = 0.003). We used ultra-high field MRI to identify areas of meningeal inflammation and to track them over time in SJL/J mice with experimental autoimmune encephalomyelitis, and then used this model to identify BTK inhibition as a novel therapeutic approach to target meningeal inflammation. The results of this study provide support for future studies in multiple sclerosis patients with imaging evidence of meningeal inflammation.
Reducing Broad-Spectrum Antimicrobial Use in Extracorporeal Membrane Oxygenation: Reduce AMMO Study
Authors: Shah Aditya , Sampathkumar Priya , Stevens Ryan W , Bohman John K , Lahr Brian D , Dhungana Prabij , Vashistha Kirtivardhan , O’Horo John C
Published: February 2021

Background

The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across 3 time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol.

Methods

In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and National Healthcare Safety Network–reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we reevaluated the same metrics.

Results

Our study population included 338 intensive care unit patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol, we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad-spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates.

Conclusions

Our final protocol significantly reduces broad-spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience.

Summary: There are no guidelines for antimicrobial prophylaxis in patients on extracorporeal membrane oxygenation (ECMO). A rational approach employing concepts of antimicrobial stewardship can drive logical antimicrobial selection for prophylaxis in patients on ECMO without adversely impacting outcomes.
Baseline Neurocognitive Impairment (NCI) Is Associated With Incident Frailty but Baseline Frailty Does Not Predict Incident NCI in Older Persons With Human Immunodeficiency Virus (HIV)
Authors: Masters Mary Clare , Perez Jeremiah , Wu Kunling , Ellis Ronald J , Goodkin Karl , Koletar Susan L , Andrade Adriana , Yang Jingyan , Brown Todd T , Palella Frank J , Sacktor Ned , Tassiopoulos Katherine , Erlandson Kristine M
Published: February 2021

Background

Neurocognitive impairment (NCI) and frailty are more prevalent among persons with human immunodeficiency virus (HIV, PWH) compared to those without HIV. Frailty and NCI often overlap with one another. Whether frailty precedes declines in neurocognitive function among PWH or vice versa has not been well established.

Methods

AIDS Clinical Trials Group (ACTG) A5322 is an observational cohort study of older PWH. Participants undergo annual assessments for NCI and frailty. ACTG A5322 participants who developed NCI as indexed by tests of impaired executive functioning and processing speed during the first 3 years were compared to persons who maintained normal cognitive function; those who demonstrated resolution of NCI were compared to those who had persistent NCI. Participants were similarly compared by frailty trajectory. We fit multinomial logistic regression models to assess associations between baseline covariates (including NCI) and frailty, and associations between baseline covariates (including frailty) and NCI.

Results

In total, 929 participants were included with a median age of 51 years (interquartile range [IQR] 46–56). At study entry, 16% had NCI, and 6% were frail. Over 3 years, 6% of participants developed NCI; 5% developed frailty. NCI was associated with development of frailty (odds ratio [OR] = 2.06; 95% confidence interval [CI] = .94, 4.48; P = .07). Further adjustment for confounding strengthened this association (OR = 2.79; 95% CI = 1.21, 6.43; P = .02). Baseline frailty however was not associated with NCI development.

Conclusions

NCI was associated with increased risk of frailty, but frailty was not associated with development of NCI. These findings suggest that the presence of NCI in PWH should prompt monitoring for the development of frailty and interventions to prevent frailty in this population.
The impact of measuring methods and normal values for assessment of left atrial size and filling pressures- an echocardiographic study of volume, area and diameter
Authors: Svedin JS , Avertoft MA , Petrini JP
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Different normal values for left atrial size are used in different hospitals, most commonly American Society of Echocardiography (ASE) and Normal Reference Range for Echocardiography (NORRE) which is recommended by a national external quality assessor.

Purpose

The aim of the study was to compare left atrial volume indexed (LAVI) by Simpson and Area-length (A-L) using the normal values of ASE and NORRE respectively as well as left atrial area and the older anterio-posterior diameter to compare the number of dilated left atria. We also wanted to use the volumes, area and diameter in an algorithm (LAVI, E/e´ and sPAP) for estimation of left ventricular filling pressures.

Material and methods

100 men and 100 women examined at the same echo lab in January 2020 were included. Measurements of volume and area were extracted, and the anterio-posterior diameter was measured. The measurements were compared with ASE and NORRE normal values and used in the algorithm to estimate the filling pressure.

Results

There was an excellent correlation between Simpson and A-L (p <0,001). For A-L there was 50 % increase in dilated left atria compared to NORRE, using Simpson the increase was 38 % (p <0,001). The correlation between Simpson and A-L gave that in LAVI 34 ml/m² according to Simpson corresponded to A-L of 37 ml/m² and 37 ml/m² according to Simpson corresponded to 40 ml/m² according to A-L.

The number of patients with elevated filling pressure was 7% for NORRES normal values of LAVI (Simpson and A-L), for ASE normal values 10 % (Simpson, ns) and 11% (A-L, p <0,05 compared to NORRE).

Using LAVI NORRE Simpson as a reference standard the sensitivity for ASE LAVI Simpson and A-L was 100 % and the specificity 75 % and 63 % respectively. The anterio-posterior diameter had the lowest sensitivity (54 %). NORRE LAVI A-L turned out with 99 % specificity and 86 % sensitivity.

Conclusion

The choice of reference values and measuring method significantly affects the number of dilated left atria but also the assessment of left filling pressures to some degree.

Abstract Figure.
Clinical and echocardiographic characteristics of patients with pathology proven left-sided non-valvular papillary fibroelastoma
Authors: El-Am E , Ahmad A , Kurmann R , Sorour A , Bois M , Maleszewski J , Klarich K
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Papillary fibroelastoma (PFE) is now regarded as the most common primary tumor of the heart. Although benign, they are clinically significant for their high risk of embolization. They are most commonly found on cardiac valves but can also be present on non-valvular endocardial surfaces.

The aim of this study was to better characterize patients with left-sided non-valvular PFE and its clinical sequelae.

Methods

We retrospectively identified patients with pathology-proven PFEs at a single center between January 1995 and December 2018 (n = 279). Patients with left-sided non-valvular PFE were analyzed. Medical records were retrospectively reviewed for clinical characteristics and outcomes. In addition, intra-operative transesophageal echocardiograms were manually reviewed to estimate overall size and location.

Results

During the study period, we identified 37 patients with left-sided non-valvular PFE (mean age 61 ± 14 years; 62% females) (Table). PFEs were located on the left ventricle in 41%, left atrium in 35%, and left ventricular outflow tract in 24% of patients. Around a quarter of patients (27%) had a diagnosis of hypertrophic cardiomyopathy, 19% had prior cardiac surgery, and 27% had cancer diagnosed prior to PFE diagnosis.

Transient ischemic attack or stroke was the presenting symptom in 22% of patients, myocardial infarction in 6% and peripheral embolization in 6%.

Median maximal length for PFE on the left ventricle was 11.1 mm [3;18], on the left atrium 9 mm [2;25], and left ventricular outflow tract 8 mm [6;13].

A minority of patients (9/37 [24%]) had associated valvular PFE on the mitral valve and/or aortic valve (1 patient had both mitral valve and aortic valve PFE, 7 had aortic valve PFE and 1 had Mitral valve PFE).

Only 13 patients had follow up transthoracic/transesophageal echocardiogram 1 year after PFE removal; 4/13 (31%) had documented PFE recurrence (3 PFE recurred in the same location as the original; 1 in a different location).

Conclusion

Left-sided non-valvular PFE is associated with thromboembolic events and at least in those that had follow-up echocardiograms, had a high recurrence rate. More studies are needed to evaluate the management of patients with asymptomatic PFE.

Abstract Figure. Baseline Characteristics
Pulmonary arterial wave reflection as a novel estimate of pulmonary vascular resistance
Authors: Hayama H , Uejima T , Okazaki T , Hara H , Hiroi Y
Published: February 2021

Funding Acknowledgements

Type of funding sources: Public hospital(s). Main funding source(s): International Medical Research and Development Fund

Background

Measuring pulmonary vascular resistance (PVR) is essential for diagnosing pulmonary hypertension. PVR can be estimated from a simple ratio of tricuspid regurgitation velocity (TRV) to time-velocity integral of flow through right ventricular outflow tract (RVOT) (Abbas equation), but this relationship has been shown to be unreliable in patients with high PVR. Once PVR is elevated, there is an increased pressure wave reflected from the peripheral of pulmonary artery (PA). We tested the hypothesis that assessing PA wave reflection could be an alternative method for estimating PVR.

Methods

This study recruited 83 patients (69 ± 14 years old, 44 men), including 41 patients with left-sided heart disease, 23 patients with pulmonary arterial hypertension and 19 patients with chronic thromboembolic pulmonary hypertension. PA wave reflection was assessed by separating PA pressure waveform derived from a Doppler tracing of TRV into forward and backward pressure (Pf and Pb), using a velocity profile at RVOT. This separation was based on the concept of wave intensity. PVR was estimated using Abbas equation. Pb and PVR by Abbas equation were compared for the correlations with direct measurement of PVR by right heart catheterisation within 48 hours after echocardiography.

Results

Figure A illustrates Pb and Pf waveforms obtained from a patient with chronic thromboembolic pulmonary hypertension. Pb increased from mid systole and formed a late peak of PA pressure waveform. Pb correlated strongly with PVR by catheter (figure B), whereas PVR by Abbas equation underestimated PVR especially when PVR was high, resulting in a moderate correlation (figure C). Receiver-operator characteristic curves showed a higher accuracy of Pb for identifying PVR > 3WU as well as 6WU, compared with PVR by Abbas equation (figure D and E).

Conclusions

This novel echocardiographic method for assessing PA wave reflection helps diagnose the severity of pulmonary hypertension.

Abstract Figure.
Left atrial function after successful catheter ablation for paroxysmal atrial fibrillation: cryoablation versus radiofrequency techniques
Authors: Pilichowska E , Sikorska A , Baran J , Piotrowski R , Krynski T , Kulakowski P , Zaborska B
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Purpose

It has been suggested that cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF) may lead to more extensive left atrial (LA) injury than radiofrequency (RF) ablation, however, results are conflicting. We sought to address this issue using modern echocardiographic techniques.

Methods

We performed transthoracic echocardiography in 90 patients (66% males, mean age 57 ± 10 years) successfully treated  with RF (51%) or CB (49%) ablation for PAF before and 6 months after the procedure. Peak longitudinal LA strain (LAS) and strain rate (LASR) during the reservoir (r), conduit (cd) and contraction (ct) phases were measured during sinus rhythm by speckle tracking. The LA diameter and volume (LAV) index - using biplane area-length method divided by the body surface area were also calculated.

Results

The LA diameter decreased (38.1 ± 4.0 vs 37.2 ± 3.8 mm, p = 0.004), the LAV index did not change (33.5 ± 11.9 vs 34.4 ± 8.9 mL/m², p = 0.272) at 6 months in the whole study group. The LASRr and LASRcd increased, whereas there were no changes in remaining LA function parameters in either ablation strategy (table). The CB subgroup did not differ in LA function parameters comparing to RF subgroup at six months after procedure (table).

Conclusion

CB and RF ablation did not differentially affect the LA function. Successful ablation for PAF resulted in improvement of  rate of deformation during reservoir and conduit LA cycle and stable contractile LA function.

LA function parameters RF N = 46 (51%) CB N = 44 (49%) 6 months RF vs CB Parameter Baseline 6 months p Baseline 6 months p p* Global LASr [%] 27.7 ± 6.35 27.9 ± 6.0 0.833 27.9 ± 7.2 27.0 ± 6.4 0.370 0.539 Global LAScd [%] -14.6 ± 4.1 -14.8 ± 4.6 0.761 -15.3 ± 5.3 -14.1 ± 3.2 0.080 0.399 Global LASct [%] -13.0 ± 4.84 -13.0 ± 3.20 1.00 -12.6 ± 3.81 -12.9 ± 4.18 0.629 0.897 Global LASRr [sˉ¹] 1.18 ± 0.22 1.27 ± 0.26 0.046 1.07 ± 0.27 1.18 ± 0.30 0.041 0.141 Global LASRcd [sˉ¹] -1.11 ± 0.33 -1.25 ± 0.35 0.013 -1.07 ± 0.31 -1.16 ± 0.30 0.044 0.214 Global LASRct [sˉ¹] -1.46 ± 0.40 -1.50 ± 0.31 0.500 -1.42 ± 0.51 -1.39 ± 0.42 0.742 0.187 *p value corrected for baseline values
Right atrial strain by speckle-tracking echocardiography as a prognostic predictor in a pulmonary hypertension cohort
Authors: Dias Ferreira Reis JP , Branco L , Nogueira M , Morais L , Sousa L , Galrinho A , Agapito A , Ferreira R
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Right atrial (RA) strain is as a promising technique for assessment of RA function and several studies have suggested it is a powerful prognostic marker in pulmonary hypertension (PH) patients (pts). Our aim was to assess the prognostic power of RA strain in Pulmonary Arterial Hypertension (PAH) and Chronic Thromboembolic Pulmonary Hypertension (CTEPH) pts.

Methods

Pts with PH were prospectively studied and several clinical/demographic/echocardiographic were retrieved as well as data from six-minute walk test (6MWT) and brain natriuretic peptide (BNP). Correlation between RA strain and other variables was tested with Pearson"s correlation analysis. Regression and survival analysis were performed to assess the combined endpoint of all-cause mortality or hospitalization in the first follow-up year (MH1).

Results

A total of 51 PH pts (mean age 54 ± 46 years, 33.3% male, baseline BNP of 342.4 ± 439.9pg/mL and baseline pulmonary artery systolic pressure – PASP - of 78 ± 26mmHg), of which 64.7% had PAH and 35.3% presented CTEPH. 19 ots (37.3%) met the primary endpoint. The mean RA strain was -21.9 ± -4.9%, with no significant difference between groups (-23.4% vs -17.8%, p = 0.150), however male pts had a significantly lower RA strain (-15.9% vs -25.1%, p = 0.014). There was a statistically significant (p < 0.05) correlation between RA strain and age (r = -0.287), indexed RA area (r = -0.539), index RA volume (r = -0.522) and right ventricular strain (r = -0.453). There was no correlation between RA strain and BNP value (p = 0.150), 6MWT distance (p = 0.145) or PASP (p = 0.072). RA strain was a predictor of MH1 (OR = 0.94, 95% CI: 0.894-0.998, p = 0.048). Pts who met the primary endpoint had a significantly worse RA strain (-17.0 vs -24.6%, p = 0.032). Those with a RA strain worse than -19% presented a significantly lower survival free of events during the first follow-up year (log rank p = 0.022).

Conclusion

RA strain is a powerful predictor of adverse events in a PH population and should be systematically assessed in order to improve risk stratification.

Abstract Figure.
Vena contracta area size predicts effectiveness of interventional edge-to-edge repair in tricuspid valve regurgitation
Authors: Goebel B , Salomon C , Awada H , Costello E , Sassenberg N , Lauten P , Lapp H
Published: February 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Percutaneous tricuspid valve edge-to-edge repair (pTVR) is a promising interventional technique for patients with tricuspid regurgitation (TR), but guidance regarding patient selection and echocardiographic screening is lacking. The aim of this study was to identify echocardiographic measurements which may predict pTVR success.

Methods

Before and after pTVR, echocardiographic data, including 3D full-volume datasets, were obtained and quantified. Right ventricular assessments included ejection fraction (RVEF3D) and diastolic (RVVd3D) and systolic (RVVs3D) volumes. Also evaluated were: right atrial (RA) volume, effective regurgitant orifice area by PISA method (EROAPISA), vena contracta area (VCA3D) by multiplanar reconstruction from a 3D colour Doppler loop (Figure 1a), maximal diastolic tricuspid annulus area from a 3D zoom image (Figure 1b), and tricuspid tenting area. TR severity was graded according to EROAPISA and VCA3D as grade 1+ to 5+.

Results

Patients (n= 44, age 72 ± 9 years, 20 male) with at least moderate to severe TR undergoing pTVR were consecutively included. The patients were divided into groups according to their post-pTVR TR grade. Group 1 had TR grade ≤2+, and group 2 had TR grade ≥3+.Echocardiographic parameters before pTVR for both groups are presented in Table 1. As expected, patients with TVR ≥3+ after pTVR had significantly worse pre-intervention echocardiographic measurements of TR severity, valve dimensions, and chamber volumes. ROC curves for the prediction of TR ≤2+ (mild to moderate) after pTVR (defined as VCA3D <0.75 cm² and EROAPISA <0.4 cm²) were drawn for different echocardiographic features (Figure 2). VCA3D by 3D colour Doppler yielded the highest area under the ROC curve followed by TV anatomy measurements (Annulus area3D, Tenting area) and right atrial volume.

Conclusion

A thorough evaluation of TR and valve dimensions by 3D echocardiography, particulary the evaluation of VCA3D by 3D colour Doppler, aids in the prediction of the probability of pTVR success.

Abstract Figure.