bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCSK9 deficiency rewires heart metabolism and drives heart failure with preserved ejection fraction
Authors: Da Dalt Lorenzo , Castiglioni Laura , Baragetti Andrea , Audano Matteo , Svecla Monika , Bonacina Fabrizia , Pedretti Silvia , Uboldi Patrizia , Benzoni Patrizia , Giannetti Federica , Barbuti Andrea , Pellegatta Fabio , Indino Serena , Donetti Elena , Sironi Luigi , Mitro Nico , Catapano Alberico Luigi , Norata Giuseppe Danilo 
Published: June 2021

Abstract

Aims
PCSK9 is secreted into the circulation, mainly by the liver, and interacts with low-density lipoprotein receptor (LDLR) homologous and non-homologous receptors, including CD36, thus favouring their intracellular degradation. As PCSK9 deficiency increases the expression of lipids and lipoprotein receptors, thus contributing to cellular lipid accumulation, we investigated whether this could affect heart metabolism and function.

Methods and results
Wild-type (WT), Pcsk9 KO, Liver conditional Pcsk9 KO and Pcsk9/Ldlr double KO male mice were fed for 20 weeks with a standard fat diet and then exercise resistance, muscle strength, and heart characteristics were evaluated. Pcsk9 KO presented reduced running resistance coupled to echocardiographic abnormalities suggestive of heart failure with preserved ejection fraction (HFpEF). Heart mitochondrial activity, following maximal coupled and uncoupled respiration, was reduced in Pcsk9 KO mice compared to WT mice and was coupled to major changes in cardiac metabolism together with increased expression of LDLR and CD36 and with lipid accumulation. A similar phenotype was observed in Pcsk9/Ldlr DKO, thus excluding a contribution for LDLR to cardiac impairment observed in Pcsk9 KO mice. Heart function profiling of the liver selective Pcsk9 KO model further excluded the involvement of circulating PCSK9 in the development of HFpEF, pointing to a possible role locally produced PCSK9. Concordantly, carriers of the R46L loss-of-function variant for PCSK9 presented increased left ventricular mass but similar ejection fraction compared to matched control subjects.

Conclusion
PCSK9 deficiency impacts cardiac lipid metabolism in an LDLR independent manner and contributes to the development of HFpEF.
Heterologous expression of equol biosynthesis genes fromAdlercreutzia equolifaciens
Authors: Vázquez Lucía , Flórez Ana Belén , Rodríguez Javier , Mayo Baltasar 
Published: June 2021

ABSTRACTEquol is the isoflavone-derived metabolite with the greatest estrogenic and antioxidant activity. It is produced from daidzein by fastidious and oxygen-susceptible intestinal bacteria, which hinders their use at an industrial scale. Therefore, expressing the equol production machinery into easily-cultivable hosts would expedite the heterologous production of this compound. In this work, four genes (racemase, tdr, ddr and dzr) coding for key enzymes involved in equol production in Adlercreutzia equolifaciens DSM19450T were synthesized and cloned in a pUC-derived vector (pUC57-equol) that was introduced in Escherichia coli. Recombinant clones of E. coli produced equol in cultures supplemented with daidzein (equol precursor) and dihydrodaidzein (intermediate compound). To check whether equol genes were expressed in Gram-positive bacteria, the pUC57-equol construct was cloned into the low-copy-number vector pIL252, and the new construct (pIL252-pUC57-equol) introduced into model strains of Lacticaseibacillus casei and Lactococcus lactis. L. casei clones carrying pIL252-pUC57-equol produced a small amount of equol from dihydrodaidzein but not from daidzein, while L. lactis recombinant clones produced no equol from either of the substrates. This is the first time that A. equolifaciens equol genes have been cloned and expressed in heterologous hosts. E. coli clones harboring pUC57-equol could be used for biotechnological production of equol.
High-Quality Genome Assembly and Comprehensive Transcriptome of the Painted Lady ButterflyVanessa cardui
Authors: Zhang Linlin , Steward Rachel A , Wheat Christopher W , Reed Robert D 
Published: June 2021

AbstractThe painted lady butterfly, Vanessa cardui, has the longest migration routes, the widest hostplant diversity, and one of the most complex wing patterns of any insect. Due to minimal culturing requirements, easily characterized wing pattern elements, and technical feasibility of CRISPR/Cas9 genome editing, V. cardui is emerging as a functional genomics model for diverse research programs. Here, we report a high-quality, annotated genome assembly of the V. cardui genome, generated using 84× coverage of PacBio long-read data, which we assembled into 205 contigs with a total length of 425.4 Mb (N50 = 10.3 Mb). The genome was very complete (single-copy complete Benchmarking Universal Single-Copy Orthologs [BUSCO] 97%), with contigs assembled into presumptive chromosomes using synteny analyses. Our annotation used embryonic, larval, and pupal transcriptomes, and 20 transcriptomes across five different wing developmental stages. Gene annotations showed a high level of accuracy and completeness, with 14,437 predicted protein-coding genes. This annotated genome assembly constitutes an important resource for diverse functional genomic studies ranging from the developmental genetic basis of butterfly color pattern, to coevolution with diverse hostplants.
On backflow associated with oceanic and continental subduction
Authors: Moulas Evangelos , Brandon Mark T , Vaughan Hammon Joshua D , Schmalholz Stefan M 
Published: June 2021

SUMMARY
A popular idea is that accretion of sediment at a subduction zone commonly leads to the formation of a subduction channel, which is envisioned as a narrow zone located above a subducting plate and filled with vigorously circulating accreted sediment and exotic blocks. The circulation can be viewed as a forced convection, with downward flow in the lower part of the channel due to entrainment by the subducting plate, and a ‘backflow’ in the upper part of the channel. The backflow is often cited as an explanation for the exhumation of high-pressure/low-temperature metamorphic rocks from depths of 30 to 50 km. Previous analyses of this problem have mainly focused on the restricted case where the walls bounding the flow are artificially held fixed and rigid. A key question is if this configuration can be sustained on a geologically relevant timescale. We address this question using a coupled pair of corner flows. The pro-corner accounts for accretion and deformation directly above the subducting plate, and the retro-corner corresponds to a deformable region in the overlying plate. The two corners share a medial boundary, which is fully coupled but is otherwise free to rotate and deform. Our results indicate that the maintenance of a stable circulating flow in a narrow pro-corner (&lt;15°) requires an unusually large viscosity ratio, μretro/μpro &gt; 103. For lower viscosity ratios, the medial boundary would rotate rearwards, converting the initially narrow pro-corner into an obtuse geometry. For a stable narrow corner, we show that the backflow within the corner is caused by downward convergence of the incoming flow and an associated downward increase in dynamic pressure, which reaches a maximum at the corner point. The total pressure is thus expected to be much greater than predicted using a lithostatic gradient, which means that estimates of depth from metamorphic pressure would have to be adjusted accordingly. In addition, we show that the velocity fields associated with a forced corner flow and a buoyancy-assisted channel flow are nearly identical. As such, structural geology studies are not sufficient to distinguish between these two processes.
SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses
Authors: Suhandynata Raymond T , Bevins Nicholas J , Tran Jenny T , Huang Deli , Hoffman Melissa A , Lund Kyle , Kelner Michael J , McLawhon Ronald W , Gonias Steven L , Nemazee David , Fitzgerald Robert L 
Published: June 2021

Abstract

Background
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 110 million individuals and led to 2.5 million deaths worldwide. As more individuals are vaccinated, the clinical performance and utility of SARS-CoV-2 serology platforms needs to be evaluated.

Methods
The ability of 4 commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 patients who were SARS-CoV-2 PCR positive, 89 SARS-CoV-2-vaccinated healthcare workers (Pfizer or Moderna), and 127 patients who were SARS-CoV-2 negative. Serology results were compared to a cell-based SARS-CoV-2 pseudovirus (PSV) neutralizing antibodies assay.

Results
The Roche S-(spike) antibody and Diazyme neutralizing antibodies (NAbs) assays detected adaptive immune response in 100.0% and 90.1% of vaccinated individuals who received 2 doses of vaccine (initial and booster), respectively. The Roche N-(nucleocapsid) antibody assay and Diazyme IgG assay did not detect adaptive immune response in vaccinated individuals. The Diazyme NAbs assay correlated with the PSV SARS-CoV-2 median infective dose (ID50) neutralization titers (R2 = 0.70), while correlation of the Roche S-antibody assay was weaker (R2 = 0.39). Median PSV SARS-CoV-2 ID50 titers more than doubled in vaccinated individuals who received 2 doses of the Moderna vaccine (ID50, 597) compared to individuals who received a single dose (ID50, 284).

Conclusions
The Roche S-antibody and Diazyme NAbs assays robustly detected adaptive immune responses in SARS-CoV-2 vaccinated individuals and SARS-CoV-2 infected individuals. The Diazyme NAbs assay strongly correlates with the PSV SARS-CoV-2 NAbs in vaccinated individuals. Understanding the reactivity of commercially available serology platforms is important when distinguishing vaccination response versus natural infection.
Strategic Decision-Making by a Forensic Toxicology Laboratory in Response to an Emerging NPS: Detection, Quantitation and Interpretation of Carfentanil in Death Investigations in Ontario, Canada, July 2017 to June 2018
Authors: Solbeck Patricia , Woodall Karen L , Martin Teri L 
Published: June 2021

Abstract
The proliferation of novel psychoactive substances (NPS) and the current opioid epidemic creates challenges for a toxicology laboratory. Methods capable of detecting and quantitating emerging compounds must be established despite limited information on toxicologically relevant concentrations. This paper will (i) describe how a publicly funded forensic laboratory reacted to the emergence of carfentanil as a public safety concern and (ii) contribute to the existing forensic literature by presenting a series of deaths involving carfentanil between July 2017 and June 2018. The Centre of Forensic Sciences is the primary provider of forensic toxicology testing in medicolegal death investigations in the province of Ontario. When carfentanil was first identified in the illicit drug supply, routine screening methods used by this laboratory were not sufficiently sensitive to detect the drug at concentrations expected in blood samples. Previously validated, multi-target liquid chromatography–tandem mass spectrometry (LC–MS-MS) quantitative methods already in use by the laboratory did show improved detectability for carfentanil. Thus, an existing LC–MS-MS method was adapted to include carfentanil, achieving improved sensitivity while also providing quantitation in suspected drug-related deaths. This approach had the added benefit that the LC–MS-MS method selected for modification was used in all death investigations requiring toxicology analysis in Ontario, thereby providing an opportunity for surveillance. Using this method, 4,953 cases were analyzed with carfentanil detected at a concentration greater than the limit of detection (0.05 ng/mL) in 160 decedents. Postmortem blood carfentanil concentrations ranged from less than 0.1 to 9.2 ng/mL. Of the 160 carfentanil-positive cases, 156 were classified as either mixed drug toxicity or carfentanil overdose. The approach described enabled this laboratory to efficiently implement a quantitative test for carfentanil in all death investigations, providing a useful template for modifying existing methods when a new psychoactive substance becomes available in the population.
The Carbon Cost of Travel to a Medical Conference: Modelling the Annual Meeting of the Canadian Association of Gastroenterology
Authors: Leddin Desmond , Galts Ciaran , McRobert Elizabeth , Igoe John , Singh Harminder , Sinclair Paul 
Published: June 2021

Abstract

Objectives
We estimated and compared the travel related carbon emissions of the annual meeting of the Canadian Association of Gastroenterology between the two most common geographical locations of the meeting.

Methods
We modelled the car, train and flight travel journey of each registrant to two annual meetings. One was held in Toronto, close to where the majority of Gastroenterogists live, the other in Banff in the west of the country. We used validated carbon emission outputs per kilometer of travel.

Results
The average per capita distance travelled to the Toronto meeting was 2845 km, resulting in 0.540 tonnes (t) of CO2equivalent (CO2e) emitted per person. When the meeting was held in Banff emissions were 41% higher than those in Toronto with an average distance travelled of 3949 km and 0.760t of CO2e emitted per person. Almost all of the travel related carbon emissions for both meetings were generated by flying.

Conclusions
Even when held close to the largest population centre, there is a large environmental impact from travel to annual meetings. Importantly, choice of meeting location has a very big impact on difference in carbon emissions. Societies need to consider the site of meetings and reduce the number of in-person attendees if they wish to reduce their carbon footprint. Hybrid models participants should be considered. Our analysis also suggests, other medical societies who wish to model their annual meetings can use a simplified model, using flying distance only, to estimate travel-related emissions.
The Galleria mellonella-Enteropathogenic Escherichia coli Model System: Characterization of Pathogen Virulence and Insect Immune Responses
Authors: Chen Robin Y , Keddie B Andrew 
Published: June 2021

Abstract
The use of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae), an economical insect model, for the study of enteropathogenic Escherichia coli (Migula) (EPEC), a diarrheagenic human pathogen, has been demonstrated previously but remains poorly understood. The present study characterizes the Galleria-EPEC system extensively for future studies using this system. We found that EPEC causes disease in G. mellonella larvae when injected intrahemocoelically but not orally. Disease manifests as increased mortality, decreased survival time, delayed pupation, decreased pupal mass, increased pupal duration, and hemocytopenia. Disease symptoms are dose-dependent and can be used as metrics for measuring EPEC virulence in future studies. The type III secretion system was only partially responsible for EPEC virulence in G. mellonella while the majority of the virulence remains unknown in origin. EPEC elicits insect anti-bacterial immune responses including melanization, hemolymph coagulation, nodulation, and phagocytosis. The immune responses were unable to control EPEC replication in the early stage of infection (≤3 h post-injection). EPEC clearance from the hemocoel does not guarantee insect survival. Overall, this study provided insights into EPEC virulence and pathogenesis in G. mellonella and identified areas of future research using this system.
Use of over-the-counter medicines by privately insured patients with common chronic conditions in South Africa
Authors: Padayachee Neelaveni , Rothberg Alan D , Truter Ilse , Butkow Neil 
Published: June 2021

Abstract

Objectives
The study measured access to commonly used over-the-counter (OTC) medicines (OTCMs) by individuals who were insured for the management of chronic diseases and considered reasons for selection of the medicines in addition to mainstream drugs usually prescribed for treatment.

Methods
Data were extracted from a large corporate database. Eligible subjects were aged ≥40 years and registered for management of one of the prevalent non-communicable diseases. Utilization of aspirin, inhaled corticosteroids and bronchodilators was assessed.

Key findings
The study population included 12 108 controls and 4149 individuals with one of 11 common chronic conditions that were categorized as metabolic, respiratory, cardiovascular or glaucoma. There was high utilization of bronchodilators in the respiratory group, possibly indicative of poor control of the primary condition and moderate access to bronchodilators by controls, possibly self-medicating for an undiagnosed chronic condition. Aspirin was not only utilized for primary or secondary prevention in the cardiovascular and metabolic groups but also appeared to be used to treat glaucoma. Bronchodilators may also have been used to treat side effects of drugs used to treat hypertension.

Conclusions
Reasons for use of OTCMs in the treatment of a chronic condition include poor control, treatment of a side-effect of a drug used to treat the chronic condition and self-medication for an undiagnosed condition. To gain further insight, insurers should routinely analyse claims and develop performance-enhancing interventions.
Three millimeter needlescopic splenectomy using three-port technique: report of three cases
Authors: Matsushita Koji , Tagaya Nobumi , Nakajima Ryuichirou , Yagi Masayuki , Obana Yuichi , Nakano Yuhei , Suzuki Junpei , Mizoguchi Masako , Yoshimura Yukino , Arai Takashi , Hasegawa Yako , Suzuki Junichi , Haku Kyokun , Arai Toshifumi , Kurosaki Tetsuya , Saito Kazuyuki 
Published: June 2021

Abstract
We report our experience with needlescopic splenectomy (NS) for the surgical treatment of idiopathic thrombocytopenic purpura using a 3-mm needlescope with three ports. One patient was male and two were females, and their mean age was 58 years. The patient was placed in the right lateral decubitus position. The first 12-mm port was introduced through the lateral margin of the left rectus abdominis muscle, and the other two 3-mm ports were inserted in the left upper quadrant. NS was performed by a standard technique under the observation of 3.3-mm needlescope. The surgical procedure was successfully completed in all the patients. The mean duration of surgery, intra-operative bleeding volume and post-operative hospital stay were 176 min, 70 ml and 4.7 days, respectively. There were no particular peri-operative complications in spite of dense adhesions or simultaneous laparoscopic procedures. Our method is safe and feasible with low morbidity and without impairing cosmetic benefits.
Ionized gas kinematics of cluster AGN at z ∼ 0.8 with KMOS
Authors: Paillalef Marcela G , Flores Hector , Demarco Ricardo , Rettura Alessando , Jaffé Yara , Lidman Chris , Nantais Julie , Puech Mathieu , Rosati Piero 
Published: June 2021

ABSTRACT
We present an integral field spectroscopy study of two active galactic nuclei (AGN) in the galaxy cluster RXJ0152–137 at z = 0.84. We have combined integrated and 3D spectra with HST images to perform a complete morpho-kinematical analysis of each galaxy. For G557, we detect narrow and broad H α and [N ii] emission. The broad H α component is redshifted by v ∼ 939 km s−1 concerning the narrow component. The kinematics analysis and VLT/FORS2 data indicate that G557 presents evidence of radial outflows. For G300, it was possible to detect only the broad H α emission. The spectral properties of both galaxies are equivalent to those of local AGN. We also compare the results obtained for each AGN with their location within the cluster. We found a possible connection of the environment with the properties inferred for each of them, and the possible interaction of G557 with an unconfirmed neighboring galaxy, for which a bridge-like structure is observed in the HST images. This work shows evidence of how the same type of AGN can show differences in their spectroscopic properties depending on the region of the cluster in which they develop, which is important to understand how the environment affects AGN and, consequently, the evolution of galaxies.
The ionized gas outflow in the Circinus galaxy: kinematics and physical conditions
Authors: Fonseca-Faria M A , Rodríguez-Ardila A , Contini M , Reynaldi V 
Published: June 2021

ABSTRACT
We employ MUSE/VLT data to study the ionized and highly ionized gas phases of the feedback in Circinus, the closest Seyfert 2 galaxy to us. The analysis of the nebular emission allowed us to detect a remarkable high-ionization gas outflow beyond the galaxy plane traced by the coronal lines [Fe vii] λ6089 and [Fe x] λ6374, extending up to 700 and 350 pc NW from the nucleus, respectively. This is the first time that the [Fe x] emission is observed at such distances from the central engine in an active galactic nucleus (AGN). The gas kinematics reveals expanding gas shells with velocities of a few hundred km s−1, spatially coincident with prominent hard X-ray emission detected by Chandra. Density and temperature sensitive line ratios show that the extended high-ionization gas is characterized by a temperature reaching 25 000 K and an electron density &gt;102 cm−3. We found that local gas excitation by shocks produced by the passage of a radio jet leads to the spectacular high-ionization emission in this object. This hypothesis is fully supported by photoionization models that account for the combined effects of the central engine and shocks. They reproduce the observed emission line spectrum at different locations inside and outside of the NW ionization cone. The energetic outflow produced by the radio jet is spatially located close to an extended molecular outflow recently reported using ALMA which suggests that they both represent different phases of the same feedback process acting on the AGN.