bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation and characterization of human embryonic stem cell-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles
Authors: Pezhouman Arash , Engel James L , Nguyen Ngoc B , Skelton Rhys J P , Gilmore William Blake , Qiao Rong , Sahoo Debashis , Zhao Peng , Elliott David A , Ardehali Reza 
Published: March 2021

AbstractAimsWe prospectively isolate and characterize first and second heart field- and nodal-like cardiomyocytes using a double reporter line from human embryonic stem cells. Our double reporter line utilizes two important transcription factors in cardiac development, TBX5 and NKX2-5. TBX5 expression marks first heart field progenitors and cardiomyocytes while NKX2-5 is expressed in nearly all myocytes of the developing heart (excluding nodal cells). We address the shortcomings of prior work in the generation of heart field-specific cardiomyocytes from induced pluripotent stem cells and provide a comprehensive early developmental transcriptomic as well as electrophysiological analyses of these three populations.Methods and resultsTranscriptional, immunocytochemical, and functional studies support the cellular identities of isolated populations based on the expression pattern of NKX2-5 and TBX5. Importantly, bulk and single-cell RNA sequencing analyses provide evidence of unique molecular signatures of isolated first and second heart field cardiomyocytes, as well as nodal-like cells. Extensive electrophysiological analyses reveal dominant atrial action potential phenotypes in first and second heart fields in alignment with our findings in single-cell RNA sequencing. Lastly, we identify two novel surface markers, POPDC2 and CORIN, that enable purification of cardiomyocytes and first heart field cardiomyocytes, respectively.ConclusionsWe describe a high-yield approach for isolation and characterization of human embryonic stem cell-derived heart field-specific and nodal-like cardiomyocytes. Obtaining enriched populations of these different cardiomyocyte subtypes increases the resolution of gene expression profiling during early cardiogenesis, arrhythmia modelling, and drug screening. This paves the way for the development of effective stem cell therapy to treat diseases that affect specific regions of the heart- or chamber-specific congenital heart defects.
Toll-like receptor 4 activation modulates pericardium–myocardium interactions in lipopolysaccharide-induced atrial arrhythmogenesis
Authors: Lin Fong-Jhih , Li Shao-Jung , Lu Yen-Yu , Wu Wen-Shiann , Chen Yao-Chang , Chen Shih-Ann , Chen Yi-Jen 
Published: March 2021

Abstract

Aims
Inflammation plays a role in the pathogenesis of atrial fibrillation (AF). Pericarditis enhanced atrial arrhythmogenesis, but the role of the pericardium remains unclear in AF. Activation of the toll-like receptor 4 (TLR4) by binding to lipopolysaccharide (LPS) promotes cardiac electrical remodelling. In this study, we hypothesized that pericarditis may induce atrial arrhythmogenesis via pericardium–myocardium interactions by TLR4 signalling.

Methods and results
Pericarditis was induced in rabbits by injecting LPS (1–2 mg/kg) into the pericardium. Conventional microelectrodes were used to record the action potentials of left atrial (LA) posterior walls (LAPWs) and LA appendages (LAAs) with and without attached pericardium in the control or pericarditis-induced rabbits. Cytokine array was used to measure the expression levels of proinflammatory cytokines in control and LPS-treated pericardium. Compared with the controls, the LPS-treated pericardium had higher expressions of IL-1α, IL-8, and MIP-1β. Rapid atrial pacing-induced burst firing in LPS-treated LAPWs and LAAs, and in control LAPWs (but not in LAAs). The incidence of pacing-induced spontaneous activity and burst firing was increased by LPS-treated pericardium but was attenuated by the control pericardium. Moreover, burst firing induced by LPS-treated pericardium was blocked upon administration of the TLR4 inhibitor, TAK-242 (100 ng/mL), ryanodine receptor inhibitor (ryanodine, 3 μM), or calmodulin kinase II inhibitor (KN-93, 1 μM).

Conclusions
Healthy and inflamed pericardium differently modulate LPS-induced atrial arrhythmogenesis. Targeting pericardium via TLR4 signalling may be a novel therapeutic strategy for AF.
Characteristics and clinical outcomes in atrial fibrillation patients classified using cluster analysis: the Fushimi AF Registry
Authors: Ogawa Hisashi , An Yoshimori , Nishi Hidehisa , Fukuda Shunichi , Ishigami Kenjiro , Ikeda Syuhei , Doi Kosuke , Ide Yuya , Hamatani Yasuhiro , Fujino Akiko , Ishii Mitsuru , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Tsuji Hikari , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Tsukahara Tetsuya , Lip Gregory Y H , Akao Masaharu ,   the Fushimi AF Registry Investigators
Published: March 2021

Abstract

Aims
The risk of adverse events in atrial fibrillation (AF) patients was commonly stratified by risk factors or clinical risk scores. Risk factors often do not occur in isolation and are often found in multimorbidity ‘clusters’ which may have prognostic implications. We aimed to perform cluster analysis in a cohort of AF patients and to assess the outcomes and prognostic implications of the identified comorbidity cluster phenotypes.

Methods and results
The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Hierarchical cluster analysis was performed on 4304 patients (mean age: 73.6 years, female; 40.3%, mean CHA2DS2-VASc score 3.37 ± 1.69), using 42 baseline clinical characteristics. On hierarchical cluster analysis, AF patients could be categorized into six statistically driven comorbidity clusters: (i) younger ages (mean age: 48.3 years) with low prevalence of risk factors and comorbidities (n = 209); (ii) elderly (mean age: 74.0 years) with low prevalence of risk factors and comorbidities (n = 1301); (iii) those with high prevalence of atherosclerotic risk factors, but without atherosclerotic disease (n = 1411); (iv) those with atherosclerotic comorbidities (n = 440); (v) those with history of any-cause stroke (n = 681); and (vi) the very elderly (mean age: 83.4 years) (n = 262). Rates of all-cause mortality and major adverse cardiovascular or neurological events can be stratified by these six identified clusters (log-rank test; P &lt; 0.001 and P &lt; 0.001, respectively).

Conclusions
We identified six clinically relevant phenotypes of AF patients on cluster analysis. These phenotypes can be associated with various types of comorbidities and associated with the incidence of clinical outcomes.

Clinical Trial Registration Information
https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.
Left femoral venous access for leadless pacemaker implantation: patient characteristics and outcomes
Authors: Jelisejevas Julius , Breitenstein Alexander , Hofer Daniel , Winnik Stephan , Steffel Jan , Saguner Ardan M 
Published: March 2021

Abstract

Aims
Leadless pacing has become an alternative approach for patients requiring a single-chamber pacemaker. Conventionally, leadless Micra Transcatheter Pacing System (TPS) pacemakers are implanted via a right femoral venous access. However, due to various reasons, a left-sided femoral venous approach may be necessary. We hypothesized that a left-sided femoral venous approach is as safe and effective when compared with a right-sided approach. We assessed indications, procedural characteristics, safety and mid-term outcomes of Micra TPS implantation via a left femoral venous approach when compared with the conventional right-sided approach.

Methods and results
In this retrospective single-centre analysis, 143 consecutive patients undergoing Micra TPS implantation were included. 87% (125/143) underwent Micra TPS implantation via a right, and 13% (18/143) via a left femoral venous access. The mean age at implantation was 79.8 ± 7.5 years. Acute procedural success, mean procedure and fluoroscopy times as well as device parameters at implantation and follow-up (mean 15 ± 11.5 months) were similar between the two groups. Five major complications (3.5%) were encountered, all using a right-sided approach. After a transfemoral TAVI procedure, left femoral venous access was used in 42% of cases when compared with 8% in the remaining population (P = 0.003).

Conclusions
A left femoral venous access for Micra TPS implantation is safe and effective with an excellent implantation success rate similar to a conventional right femoral venous access without longer implantation and fluoroscopy times. The most frequent reason for choosing left vs. right femoral venous access was a previous transfemoral TAVI procedure.
Composition and structure of the skin microbiota of rorquals off the Eastern South Pacific
Authors: Toro Frederick , Alarcón Jaime , Márquez Sebastián , Capella Juan , Bahamonde Paulina , Esperón Fernando , Moreno-Switt Andrea , Castro-Nallar Eduardo 
Published: March 2021

ABSTRACTRecent advances in high-throughput sequencing have enabled the large-scale interrogation of microbiota in the most diverse environments, including host-associated microbiota. This has led to the recognition that the skin microbiota of rorquals is specific and structurally different from that of the ocean. This study reveals the skin microbiome of 85 wild individuals along the Chilean coast belonging to Megaptera novaeangliae, Balaenoptera musculus and Balaenoptera physalus. Alpha diversity analysis revealed significant differences in richness and phylogenetic diversity, particularly among humpback whales from different locations and between blue and humpback whales. Beta diversity was partially explained by host and location but only accounting for up to 17% of microbiota variability (adjusted VPA). Overall, we found that microbiota composition was dominated by bacterial genera such as Cardiobacter, Moraxella, Tenacibaculum, Stenotrophomonas, Flavobacteria and Pseudomonas. We also found that no ASVs were associated with the three rorqual species. Up to four ASVs were specific of a location, indicating a great variability in the microbiota. To the best of our knowledge, this is the first report on the composition and structure of the skin microbiota of whales off the coast of Chile, providing a foundational dataset to understand the microbiota's role in rorquals.
The paradox of China’s tobacco industry: competition through monopoly policy
Authors: Liao Allen , Cole Benjamin 
Published: March 2021

Abstract
This study documents the evolution of China’s tobacco industry over 70 years from that of unordered local trade to ordered competitive national industry. We develop a theoretical framework regarding three levers the central government utilized—quota pliability, price tiering, and public rankings—to shift the attention of producers from merely fulfilling quotas to seeking quota partners, building scale economies, and developing high quality brands. The findings provide insights to those interested in planned economies, industry dynamics, and China’s industrial development.
DNA/RNA metabarcoding and morphological analysis of epipelagic copepod communities in the Izu Ridge off the southern coast of Japan
Authors: Hirai Junya , Hidaka Kiyotaka , Nagai Satoshi , Shimizu Yugo 
Published: March 2021

AbstractThe Izu Ridge off the southern coast of Japan is composed of many seamounts and knolls and is an important fishery ground and hatchery for commercially important fish. As pelagic copepods link lower and higher trophic levels, we investigated the epipelagic copepods in the Izu Ridge using 28S DNA/RNA metabarcoding and microscopic approaches. In comparison with off-ridge regions, a low water temperature and high chlorophyll a concentration were observed in the Izu Ridge, possibly attributed to high levels of nutrients supplied by strong turbulences around the complex topography. We observed unique copepod communities with a large total biomass in the Izu Ridge, owing to the increased dominance of large copepod species. rRNA:rDNA (28S ratio) of these large species mainly showed positive correlations with the chlorophyll a concentration, suggesting a rapid response to the food supply. Migrating copepods were less dominant around the Izu Ridge with a shallow water depth. Higher species diversity and more rare species were detected in the Izu Ridge, which might be maintained by complex environment conditions including temporal and spatial variations in the concentration of chlorophyll a. Thus, the combined approach characterized copepod community structure and diversity supporting the rich pelagic ecosystems in the Izu Ridge.
Characterization of Human Immunodeficiency Virus (HIV) Infection in Cisgender Men and Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083
Authors: Marzinke Mark A , Grinsztejn Beatriz , Fogel Jessica M , Piwowar-Manning Estelle , Li Maoji , Weng Lei , McCauley Marybeth , Cummings Vanessa , Ahmed Shahnaz , Haines Casey D , Bushman Lane R , Petropoulos Christos , Persaud Deborah , Adeyeye Adeola , Kofron Ryan , Rinehart Alex , St Clair Marty , Rooney James F , Pryluka Daniel , Coelho Lara , Gaur Aditya , Middelkoop Keren , Phanuphak Nittaya , Cohen Myron S , Hendrix Craig W , Anderson Peter , Hanscom Brett , Donnell Deborah , Landovitz Raphael J , Eshleman Susan H 
Published: March 2021

Abstract

Background
The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate–emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with men. We characterized HIV infections that occurred in the blinded phase of HPTN 083.

Methods
Retrospective testing included HIV testing, viral load testing, quantification of study drugs, and HIV drug resistance testing.

Results
Fifty-eight infections were evaluated, including 51 incident infections (12 in CAB arm and 39 in TDF/FTC arm). In many cases (5 in CAB arm and 37 in TDF/FTC arm), infection was associated with low or unquantifiable study drug concentrations. In 4 cases, infection occurred with on-time CAB-LA injections and expected plasma CAB concentrations. CAB exposure was associated with prolonged viral suppression and delayed antibody expression. In some cases, delayed HIV diagnosis resulted in CAB provision to participants with undetected infection, delayed antiretroviral therapy, and emergence of drug resistance; most of these infections would have been detected earlier with viral load testing.

Conclusions
Early detection of HIV infection and prompt antiretroviral therapy initiation could improve clinical outcomes in persons who become infected despite CAB-LA prophylaxis. Further studies are needed to elucidate the correlates of HIV protection in persons receiving CAB-LA.
Direct and specific binding of cholesterol to the mitochondrial translocator protein (TSPO) using PhotoClick cholesterol analogue
Authors: Georges Elias , Sottas Chantal , Li Yuchang , Papadopoulos Vassilios 
Published: March 2021

Abstract
The translocator protein (TSPO) is a five-helix transmembrane protein localized to the outer mitochondria membrane. Radioligand binding assays and chemical crosslinking showed TSPO to be a high affinity cholesterol-binding protein. In this report, we show that TSPO in mitochondrial fractions from MA-10 mouse tumour Leydig cells can interact directly and competitively with the clickable photoreactive cholesterol analogue. PhotoClick cholesterol showed saturable photoaffinity labelling of TSPO that could be specifically immunoprecipitated with anti-TSPO antibody, following the click reaction with the fluorescent-azide probe, tetramethylrhodamine (TAMRA)-azide. Moreover, excess cholesterol reduced the photolabelling of both total mitochondrial proteins and TSPO. Together, the results of this study demonstrated direct binding of PhotoClick cholesterol to TSPO and that this interaction occurs at physiologically relevant site(s).
U.S. Navy Aircraft Carrier Prevents Outbreak at Sea in Midst of COVID-19
Authors: Bigornia Veronica E 
Published: March 2021

ABSTRACT

Background
The USS Harry S Truman Strike Group deployed from Norfolk, VA in November 2019 with a crew of 5,461 personnel and successfully returned to home port in June 2020 with zero cases of COVID-19.

Methods
Senior Medical Officer’s observations and description of the evolution of the pandemic, impact to the crew of the USS Harry S Truman, a nuclear-powered aircraft carrier, and the public health principles and outbreak prevention protocols used to prevent an outbreak at sea.

Results
The USS Harry S Truman Carrier Strike Group was composed of 4,810 personnel from Carrier Strike Group 8, Harry S Truman, Destroyer Squadron 28, and Carrier Air Wing One. The medical department of 52 personnel was made up of doctors, physician assistants, nurses, independent duty corpsman, and hospital corpsman. Our escorts were one destroyer, crew size 308 and one cruiser, crew size 343, each with one independent duty corpsman and one hospital corpsman for medical staff. The total number of personnel was 5,461, all of whom returned to home port with no cases of COVID-19.

Conclusions
Outbreak with a respiratory pathogen in the shipboard environment could debilitate a crew and decrease mission effectiveness of a US Navy warship with implications to national security. Prevention of an outbreak at sea requires identification and mitigation of vulnerabilities, testing capability for identification of the pathogen, preparation for quarantine and isolation for immediate containment, and commitment from the entire crew for success.
Collision rates of planetesimals near mean-motion resonances
Authors: Wallace Spencer C , Quinn Thomas R , Boley Aaron C 
Published: March 2021

ABSTRACT
In circumstellar discs, collisional grinding of planetesimals produces second-generation dust. While it remains unclear whether this ever becomes a major component of the total dust content, the presence of such dust, and potentially the substructure within it, can be used to explore a disc’s physical conditions. A perturbing planet produces non-axisymmetric structures and gaps in the dust, regardless of its origin. The dynamics of planetesimals, however, will be very different than that of small dust grains due to weaker gas interactions. Therefore, planetesimal collisions could create dusty disc structures that would not exist otherwise. In this work, we use N-body simulations to investigate the collision rate profile of planetesimals near mean-motion resonances. We find that a distinct bump or dip feature is produced in the collision profile, the presence of which depends on the libration width of the resonance and the separation between the peri- and apocentre distances of the edges of the resonance. The presence of one of these two features depends on the mass and eccentricity of the planet. Assuming that the radial dust emission traces the planetesimal collision profile, the presence of a bump or dip feature in the dust emission at the 2:1 mean-motion resonance can constrain the orbital properties of the perturbing planet. This assumption is valid, so long as radial drift does not play a significant role during the collisional cascade process. Under this assumption, these features in the dust emission should be marginally observable in nearby protoplanetary discs with ALMA.
ALMA–IRDC: dense gas mass distribution from cloud to core scales
Authors: Barnes A T , Henshaw J D , Fontani F , Pineda J E , Cosentino G , Tan J C , Caselli P , Jiménez-Serra I , Law C Y , Avison A , Bigiel F , Feng S , Kong S , Longmore S N , Moser L , Parker R J , Sánchez-Monge Á , Wang K 
Published: March 2021

ABSTRACT
Infrared dark clouds (IRDCs) are potential hosts of the elusive early phases of high mass star formation (HMSF). Here, we conduct an in-depth analysis of the fragmentation properties of a sample of 10 IRDCs, which have been highlighted as some of the best candidates to study HMSF within the Milky Way. To do so, we have obtained a set of large mosaics covering these IRDCs with Atacama Large Millimeter/submillimeter Array (ALMA) at Band 3 (or 3 mm). These observations have a high angular resolution (∼3 arcsec; ∼0.05 pc), and high continuum and spectral line sensitivity (∼0.15 mJy beam−1 and ∼0.2 K per 0.1 km s−1 channel at the N2H+ (1 − 0) transition). From the dust continuum emission, we identify 96 cores ranging from low to high mass (M = 3.4−50.9 M⊙) that are gravitationally bound (αvir = 0.3−1.3) and which would require magnetic field strengths of B = 0.3−1.0 mG to be in virial equilibrium. We combine these results with a homogenized catalogue of literature cores to recover the hierarchical structure within these clouds over four orders of magnitude in spatial scale (0.01–10 pc). Using supplementary observations at an even higher angular resolution, we find that the smallest fragments (&lt;0.02 pc) within this hierarchy do not currently have the mass and/or the density required to form high-mass stars. None the less, the new ALMA observations presented in this paper have facilitated the identification of 19 (6 quiescent and 13 star-forming) cores that retain &gt;16 M⊙ without further fragmentation. These high-mass cores contain trans-sonic non-thermal motions, are kinematically sub-virial, and require moderate magnetic field strengths for support against collapse. The identification of these potential sites of HMSF represents a key step in allowing us to test the predictions from high-mass star and cluster formation theories.
Low-mass compact elliptical galaxies: spatially resolved stellar populations and kinematics with the Keck Cosmic Web Imager
Authors: Ferré-Mateu Anna , Durré Mark , Forbes Duncan A , Romanowsky Aaron J , Alabi Adebusola , Brodie Jean P , McDermid Richard M 
Published: March 2021

ABSTRACT
We present spatially resolved two-dimensional maps and radial trends of the stellar populations and kinematics for a sample of six compact elliptical galaxies (cE) using spectroscopy from the Keck Cosmic Web Imager (KCWI). We recover their star formation histories, finding that all except one of our cEs are old and metal rich, with both age and metallicity decreasing toward their outer radii. We also use the integrated values within one effective radius to study different scaling relations. Comparing our cEs with others from the literature and from simulations we reveal the formation channel that these galaxies might have followed. All our cEs are fast rotators, with relatively high rotation values given their low ellipticites. In general, the properties of our cEs are very similar to those seen in the cores of more massive galaxies, and in particular, to massive compact galaxies. Five out of our six cEs are the result of stripping a more massive (compact or extended) galaxy, and only one cE is compatible with having been formed intrinsically as the low-mass compact object that we see today. These results further confirm that cEs are a mixed-bag of galaxies that can be formed following different formation channels, reporting for the first time an evolutionary link within the realm of compact galaxies (at all stellar masses).