bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAMTS16 activates latent TGF-β, accentuating fibrosis and dysfunction of the pressure-overloaded heart
Authors: Yao Yufeng , Hu Changqing , Song Qixue , Li Yong , Da Xingwen , Yu Yubin , Li Hui , Clark Ian M , Chen Qiuyun , Wang Qing K 
Published: July 2019

Abstract

Aims
Cardiac fibrosis is a major cause of heart failure (HF), and mediated by the differentiation of cardiac fibroblasts into myofibroblasts. However, limited tools are available to block cardiac fibrosis. ADAMTS16 is a member of the ADAMTS superfamily of extracellular protease enzymes involved in extracellular matrix (ECM) degradation and remodelling. In this study, we aimed to establish ADAMTS16 as a key regulator of cardiac fibrosis.

Methods and results
Western blot and qRT–PCR analyses demonstrated that ADAMTS16 was significantly up-regulated in mice with transverse aortic constriction (TAC) associated with left ventricular hypertrophy and HF, which was correlated with increased expression of Mmp2, Mmp9, Col1a1, and Col3a1. Overexpression of ADAMTS16 accelerated the AngII-induced activation of cardiac fibroblasts into myofibroblasts. Protein structural analysis and co-immunoprecipitation revealed that ADAMTS16 interacted with the latency-associated peptide (LAP)-transforming growth factor (TGF)-β via a RRFR motif. Overexpression of ADAMTS16 induced the activation of TGF-β in cardiac fibroblasts; however, the effects were blocked by a mutation of the RRFR motif to IIFI, knockdown of Adamts16 expression, or a TGF-β-neutralizing antibody (ΝAb). The RRFR tetrapeptide, but not control IIFI peptide, blocked the interaction between ADAMTS16 and LAP-TGF-β, and accelerated the activation of TGF-β in cardiac fibroblasts. In TAC mice, the RRFR tetrapeptide aggravated cardiac fibrosis and hypertrophy by up-regulation of ECM proteins, activation of TGF-β, and increased SMAD2/SMAD3 signalling, however, the effects were blocked by TGF-β-NAb.

Conclusion
ADAMTS16 promotes cardiac fibrosis, cardiac hypertrophy, and HF by facilitating cardiac fibroblasts activation via interacting with and activating LAP-TGF-β signalling. The RRFR motif of ADAMTS16 disrupts the interaction between ADAMTS16 and LAP-TGF-β, activates TGF-β, and aggravated cardiac fibrosis and hypertrophy. This study identifies a novel regulator of TGF-β signalling and cardiac fibrosis, and provides a new target for the development of therapeutic treatment of cardiac fibrosis and HF.
Plaque burden can be assessed using intravascular optical coherence tomography and a dedicated automated processing algorithm: a comparison study with intravascular ultrasound
Authors: Gerbaud Edouard , Weisz Giora , Tanaka Atsushi , Luu Romain , Osman Hany Ahmed Salaheldin Hussein , Baldwin Grace , Coste Pierre , Cognet Laurent , Waxman Sergio , Zheng Hui , Moses Jeffrey W , Mintz Gary S , Akasaka Takashi , Maehara Akiko , Tearney Guillermo J 
Published: July 2019

Abstract

Aims
Plaque burden (PB) measurement using intravascular optical coherence tomography (IVOCT) is currently thought to be inferior to intravascular ultrasound (IVUS). We developed an automated IVOCT image processing algorithm to enhance the external elastic lamina (EEL) contour. Thus, we investigated the accuracies of standard IVOCT and an IVOCT enhancement algorithm for measuring PB using IVUS as the reference standard.

Methods and results
The EEL-enhancement algorithm combined adaptive attenuation compensation, exponentiation, angular registration, and image averaging using three sequential frames. In two different laboratories with intravascular imaging expertise, PB was quantified on 200 randomized, matched IVOCT and IVUS images by four independent observers. Fibroatheroma, fibrocalcific plaque, fibrous plaque, pathological intimal thickening (PIT), and mixed plaque were included in each set. Pearson’s correlation coefficients between IVUS and standard IVOCT measurements of PB were 0.61, 0.67, 0.76, 0.78, and 0.87 for fibroatheromas, mixed plaques, fibrocalcific plaques, fibrous plaques, and PIT plaques, respectively. Pearson’s correlation coefficients increased to 0.81, 0.83, 0.83, 0.84, and 0.90 when using the EEL-enhanced images (P = 0.003, P = 0.004, P = 0.08, P = 0.12, and P = 0.23, respectively). EEL-enhanced IVOCT analysis was associated with a lower EEL-area measurement absolute error for fibroatheromas, mixed plaques, and all pooled plaques (P = 0.006, P = 0.02, and P &lt; 0.001, respectively). Compared with standard IVOCT, the EEL-enhanced IVOCT images had a higher sensitivity (79% vs. 28%, P &lt; 0.001) and specificity (98% vs. 85%, P = 0.03) for plaques with an IVUS PB ≥70%.

Conclusion
EEL-enhanced IVOCT can be used to reliably measure PB in all types of coronary atherosclerotic lesions, including fibroatheromas and mixed plaques.
Spontaneous coronary artery dissection of the proximal left circumflex artery: a case report
Authors: Pineda Aleksandra , Martin Josh , Puri Aniket , Jahangiri Bijan 
Published: July 2019

Abstract

Background
Spontaneous coronary artery dissection (SCAD) has gained attention as an important cause of acute coronary syndrome and sudden cardiac death (SCD) among women. Management strategies of SCAD differ from those of atherosclerotic disease. There is an elevated risk of complications and suboptimal outcomes in patients with SCAD undergoing percutaneous coronary interventions (PCIs).

Case summary
A 48-year-old woman without any traditional cardiovascular risk factors was admitted with severe central chest pain with associated dyspnoea and diaphoresis. The patient had a strong family history of SCD, affecting three female members in their 40s and 50s. Cardiac troponins were elevated. Coronary angiogram showed moderate to severe stenosis of the proximal circumflex coronary artery. Optical coherence tomography confirmed SCAD with sub-intimal haematoma. Despite significant stenosis in the proximal segment of a relatively large artery, a decision was made not to proceed with PCI. The follow-up angiogram demonstrated normal coronaries. Magnetic resonance imaging of renal arteries showed features suggestive of fibromuscular dysplasia affecting the right renal artery. Subsequent genetic counselling and gene testing were unremarkable.

Discussion
Conservative management of SCAD is recommended because the large majority of SCAD lesions heal naturally, whereas PCI is associated with increased risk of complications and adverse outcomes. Whether SCAD is associated with the sudden death events in our patient’s family remains unclear. It certainly raises concerns as to an inheritable condition. In the absence of post-mortem findings in her family members, we can only speculate about this representing a possible inheritable form of SCAD.
Myocardial protection: a forgotten modality
Authors: Allen Bradley S 
Published: July 2019

SummaryThe goals of a cardiac surgical procedure are both technical excellence and complete protection of cardiac function. Cardioplegia is used almost universally to protect the heart and provide a quiet bloodless field for surgical accuracy. Yet, despite the importance of myocardial protection in cardiac surgery, manuscripts or dedicated sessions at major meetings on this subject have become relatively rare, as though contemporary techniques now make them unnecessary. Nevertheless, septal dysfunction and haemodynamic support (inotropes, intra-aortic balloon pump, assist devices) are common in postoperative patients, indicating that myocardial damage following cardiac surgery is still prevalent with current cardioplegic techniques and solutions. This article first describes why cardiac enzymes and septal function are the ideal markers for determining the adequacy of myocardial protection. It also describes the underappreciated consequences of postoperative cardiac enzyme release or septal dysfunction (which currently occurs in 40–80% of patients) from inadequate protection, and how they directly correlate with early and especially late mortality. Finally, it reviews the various myocardial protection techniques available to provide a detailed understanding of the cardioplegic methods that can be utilized to protect the heart. This will allow surgeons to critically assess their current method of protection and, if needed, make necessary changes to provide their patients with optimal protection.
How Do Women and Men Use Extra Time? Housework and Childcare after the French 35-Hour Workweek Regulation
Authors: Pailhé Ariane , Solaz Anne , Souletie Arthur 
Published: July 2019

Abstract
This paper analyses how and when men and women devote their extra time to childcare and housework by exploiting an exogenous shock in scheduling: the partial implementation of the 35-hour workweek reform in France. Using propensity score matching and the most recent time use survey (INSEE, 2010), we show that time reallocations differ by gender and day of the week. While men dedicate their extra time to performing more housework on weekdays in the form of mainly time-flexible tasks such as repairs or shopping, they do less on weekends. This shift from weekends to weekdays is not observed for women who perform day-to-day tasks that are less transferable. Women spend more time on childcare and reduce multitasking. Overall, task specialization by gender is more pronounced, and this gendered use of similar extra time illustrates that time allocation is not only a question of time availability. In particular, men and women ‘do gender’ at weekends, when performing tasks is more visible to others.
Restitution and adaptation measurements for the estimate of short-term cardiac action potential memory: comparison of five human ventricular models
Authors: Zaniboni Massimiliano , Cacciani Francesca 
Published: July 2019

Abstract

Aims
This computational study refines our recently published pacing protocol to measure short-term memory (STM) of cardiac action potential (AP), and apply it to five numerical models of human ventricular AP.

Methods and results
Several formulations of electrical restitution (ER) have been provided over the years, including standard, beat-to-beat, dynamic, steady-state, which make it difficult to compare results from different studies. We discuss here the notion of dynamic ER (dER) by relating it to its steady-state counterpart, and propose a pacing protocol based on dER to measure STM under periodically varying pacing cycle length (CL). Under high and highly variable-pacing rate, all models develop STM, which can be measured over the entire sequence by means of dER. Short-term memory can also be measured on a beat-to-beat basis by estimating action potential duration (APD) adaptation after clamping CL constant. We visualize STM as a phase shift between action potential (AP) parameters over consecutive cycles of CL oscillations, and show that delay between CL and APD oscillation is nearly constant (around 92 ms) in the five models, despite variability in their intrinsic AP properties.

Conclusion
dER, as we define it and together with other approaches described in the study, provides an univocal way to measure STM under extreme cardiac pacing conditions. Given the relevance of AP memory for repolarization dynamics and stability, STM should be considered, among other usual biomarkers, to validate and tune cardiac AP models. The possibility of extending the method to in vivo cellular and whole organ models can also be profitably explored.
Aerobic anoxygenic phototrophs are highly abundant in hypertrophic and polyhumic waters
Authors: Szabó-Tugyi Nóra , Vörös Lajos , V.-Balogh Katalin , Botta-Dukát Zoltán , Bernát Gábor , Schmera Dénes , Somogyi Boglárka 
Published: July 2019

ABSTRACTAerobic anoxygenic phototrophs (AAPs) are a group of photoheterotrophic bacteria common in natural waters. Here, AAP abundance and contribution to total bacterial abundance and biomass were investigated to test whether the trophic status of a lake or content of coloured dissolved organic matter (CDOM) play a role in determining AAP distribution and abundance in shallow inland lakes, with special focus on hypertrophic and polyhumic waters. Twenty-six different shallow lakes in Hungary were monitored. AAP abundance and biomass were determined by epifluorescence microscopy. The lakes exhibit a broad range of CDOM (2–7000 mg Pt L−1) and phytoplankton biomass (2–1200 μg L−1 chlorophyll a concentration). Very high AAP abundance (up to 3 × 107 cells mL−1) was observed in polyhumic and hypertrophic shallow lakes. AAP abundance was influenced by phytoplankton biomass and CDOM content, and these effects were interrelated. As determined, 40 μg L−1 chlorophyll a and 52 mg Pt L−1 CDOM are threshold levels above which these effects have a synergistic relationship. Hence, the observed high AAP abundance in some soda pans is a consequence of combined hypertrophy and high CDOM content. AAP contribution was influenced by total suspended solids (TSS) content: the success of AAP cells could be explained by high TSS levels, which might be explained by the decrease of their selective grazing control.
Fluorescent signals associated with respiratory Complex I revealed conformational changes in the catalytic site
Authors: Verkhovskaya Marina , Belevich Nikolai 
Published: July 2019

ABSTRACT
Fluorescent signals associated with Complex I (NADH:ubiquinone oxidoreductase type I) upon its reduction by NADH without added acceptors and upon NADH:ubiquinone oxidoreduction were studied. Two Complex I-associated redox-dependent signals were observed: with maximum emission at 400 nm (λex = 320 nm) and 526 nm (λex = 450 nm). The 400 nm signal derived from ubiquinol accumulated in Complex I/DDM (n-dodecyl β-D-maltopyranoside) micelles. The 526 nm redox signal unexpectedly derives mainly from FMN (flavin mononucleotide), whose fluorescence in oxidized protein is fully quenched, but arises transiently upon reduction of Complex I by NADH. The paradoxical flare-up of FMN fluorescence is discussed in terms of conformational changes in the catalytic site upon NADH binding. The difficulties in revealing semiquinone fluorescent signal are considered.
Atypical chromosome 22q11.2 deletions are complex rearrangements and have different mechanistic origins
Authors: Vervoort Lisanne , Demaerel Wolfram , Rengifo Laura Y , Odrzywolski Adrian , Vergaelen Elfi , Hestand Matthew S , Breckpot Jeroen , Devriendt Koen , Swillen Ann , McDonald-McGinn Donna M , Fiksinski Ania M , Zinkstok Janneke R , Morrow Bernice E , Heung Tracy , Vorstman Jacob A S , Bassett Anne S , Chow Eva W C , Shashi Vandana ,   International 22q11.2 Brain,   Behavior Consortium, Vermeesch Joris R 
Published: July 2019

Abstract
The majority (99%) of individuals with 22q11.2 deletion syndrome (22q11.2DS) have a deletion that is caused by non-allelic homologous recombination between two of four low copy repeat clusters on chromosome 22q11.2 (LCR22s). However, in a small subset of patients, atypical deletions are observed with at least one deletion breakpoint within unique sequence between the LCR22s. The position of the chromosome breakpoints and the mechanisms driving those atypical deletions remain poorly studied. Our large-scale, whole genome sequencing study of &gt;1500 subjects with 22q11.2DS identified six unrelated individuals with atypical deletions of different types. Using a combination of whole genome sequencing data and fiber-fluorescence in situ hybridization, we mapped the rearranged alleles in these subjects. In four of them, the distal breakpoints mapped within one of the LCR22s and we found that the deletions likely occurred by replication-based mechanisms. Interestingly, in two of them, an inversion probably preceded inter-chromosomal ‘allelic’ homologous recombination between differently oriented LCR22-D alleles. Inversion associated allelic homologous recombination (AHR) may well be a common mechanism driving (atypical) deletions on 22q11.2.
Optimization of Sludge Fermentation for Volatile Fatty Acids Production
Authors: Salamah Sultan K , Randall Andrew A 
Published: July 2019

AbstractPrefermentation of primary solids can produce volatile fatty acids (VFAs), and operational strategies may affect the propionic acid content. In this study, three prefermenter phases were used to optimize VFAs using three separate strategies. The phases were (i) glycerol (biodiesel by-product) co-fermentation with primary solids, (ii) the effect of mixing energy on the co-fermentation of glycerol and primary solids and (iii) the effect of hydrogen gas addition on the co-fermentation of glycerol and primary solids. The Phase 1 data showed that glycerol increased the VFAs production 1.2× over the possible value from the added glycerol alone (427 mg-COD/l), implying that the glycerol addition stimulated additional fermentation of primary solids. In Phase 2, low mixing energy in glycerol increased the VFAs production by 80% while slightly favoring propionic acid over acetic acid compared to the higher mixing energy. The addition of hydrogen gas in Phase 3 did not increase the VFAs total production but significantly increased the concentration of propionic acid by 41%. All three optimization approaches performed well and were able to increase the VFAs production and/or increase propionic acid concentration relative to acetic acid.
Serum Lipocalin 2 (Neutrophil Gelatinase–Associated Lipocalin) in Relation to Biomarkers of Inflammation and Cardiac Stretch During Activation of the Renin-Angiotensin-Aldosterone System in Human Immunodeficiency Virus
Authors: Bogorodskaya Milana , Fitch Kathleen V , Burdo Tricia H , Maehler Patrick , Easly Rebecca M , Murray Gillian R , Feldpausch Meghan , Adler Gail K , Grinspoon Steven K , Srinivasa Suman 
Published: July 2019

Abstract

Purpose
To evaluate the relationship of lipocalin 2 to inflammation and cardiac injury with increased aldosterone in human immunodeficiency virus (HIV).

Methods
A standardized 6-day low-sodium diet was used to stimulate renin-angiotensin-aldosterone system (RAAS) activation, and serum lipocalin 2 and biomarkers of inflammation and cardiac stretch were assessed among persons with or without HIV.

Results
Lipocalin 2 levels increased with RAAS activation compared with suppression in the HIV group (median level [interquartile range], 71.3 [59.2–99.7] vs 67.0 [51.8–86.3] ng/mL; P = .01). During RAAS activation, lipocalin 2 was related to biomarkers of inflammation (tumor necrosis factor α [P = .007]), monocyte/macrophage activation (soluble CD163 [P = .005] and chemokine [C-C motif] ligand 2 [P = .03]), and markers of cardiac stretch (brain natriuretic peptide [P < .001] and N-terminal fragment of the prohormone brain natriuretic peptide [P = .001]) in HIV.

Conclusion
Lipocalin 2 may be important in modulating aldosterone-induced inflammation, monocyte activation, and cardiac stretch during RAAS activation in HIV.

Clinical Trial Registration
NCT01407237
Hypertension and diabetes mellitus as risk factors for asthma in Korean adults: the Sixth Korea National Health and Nutrition Examination Survey
Authors: Lee Kyung Hee , Lee Hea Shoon 
Published: July 2019

Abstract

Background
Asthma is a chronic inflammatory disease that may associate with other chronic diseases such as hypertension and diabetes. We observed the effects of blood pressure (BP), fasting blood glucose (FBG), haemoglobin A1c (HbA1c) and insulin on asthma in Korean adults.

Methods
Data from 5045 adults were taken from the 2015 Sixth Korea National Health and Nutrition Examination Survey and analysed using a multiple logistic regression model.

Results
By age, the probability of asthma occurrence was 1.02 times higher (adjusted odds ratio [aOR] 1.02 [95% CI 1.01 to 1.03]). Specifically, asthma occurrence was increased in individuals &gt;66 years of age (aOR 2.40 [95% CI 1.22 to 4.72]). The probability of asthma occurrence in females was higher than in males (aOR 1.73 [95% CI 1.02 to 2.84]). Hypertension and systolic blood pressure (SBP) were found to increase the probability of asthma occurrence by 1.43- and 1.03-fold, respectively. Diabetes mellitus (DM) was another factor that increased with the occurrence of asthma (aOR 1.75 [95% CI 1.06 to 3.02]). The probability of asthma occurrence was not increased with the FBG level, whereas HbA1c (aOR 1.38 [95% CI 1.03 to 1.84]) and insulin levels (aOR 1.02 [95% CI 1.01 to 1.04]) were shown to increase the occurrence of asthma.

Conclusions
Age, sex, hypertension, SBP, DM, HbA1c and insulin levels are all factors that may influence the occurrence of asthma in Korean adults. In particular, hypertension and diabetes emerge from the present study as potential associated factors for the development of asthma.
A single amino acid substitution (H451Y) in Leishmania calcium-dependent kinase SCAMK confers high tolerance and resistance to antimony
Authors: Vergnes Baptiste , Gazanion Elodie , Mariac Cédric , Du Manoir Miléna , Sollelis Lauriane , Lopez-Rubio José-Juan , Sterkers Yvon , Bañuls Anne-Laure 
Published: July 2019

Abstract

Background
For almost a century, antimonials have remained the first-line drugs for the treatment of leishmaniasis. However, little is known about their mode of action and clinical resistance mechanisms.

Objectives
We have previously shown that Leishmania nicotinamidase (PNC1) is an essential enzyme for parasite NAD+ homeostasis and virulence in vivo. Here, we found that parasites lacking the pnc1 gene (Δpnc1) are hypersusceptible to the active form of antimony (SbIII) and used these mutant parasites to better understand antimony’s mode of action and the mechanisms leading to resistance.

Methods
SbIII-resistant WT and Δpnc1 parasites were selected in vitro by a stepwise selection method. NAD(H)/NADP(H) dosages and quantitative RT–PCR experiments were performed to explain the susceptibility differences observed between strains. WGS and a marker-free CRISPR/Cas9 base-editing approach were used to identify and validate the role of a new resistance mutation.

Results
NAD+-depleted Δpnc1 parasites were highly susceptible to SbIII and this phenotype could be rescued by NAD+ precursor or trypanothione precursor supplementation. Δpnc1 parasites could become resistant to SbIII by an unknown mechanism. WGS revealed a unique amino acid substitution (H451Y) in an EF-hand domain of an orphan calcium-dependent kinase, recently named SCAMK. When introduced into a WT reference strain by base editing, the H451Y mutation allowed Leishmania parasites to survive at extreme concentrations of SbIII, potentiating the rapid emergence of resistant parasites.

Conclusions
These results establish that Leishmania SCAMK is a new central hub of antimony’s mode of action and resistance development, and uncover the importance of drug tolerance mutations in the evolution of parasite drug resistance.
Natural disasters and trade: the mitigating impact of port substitution
Authors: Hamano Masashige , Vermeulen Wessel N 
Published: July 2019

Abstract
We study the effect of natural disasters on port-level exports. We model the interaction between firms and ports to study how strongly exports from one port are affected by changes in the cost of exporting at neighboring ports. We extend the standard trade model with heterogeneous firms to a multiple port structure where exporting is subject to port specific local transportation costs, port specific fixed export costs and international bilateral trade costs. We show that gravity distortion due to firm heterogeneity is conditional on the comparative advantage at the port level and resulting substitution of exports across ports. We present evidence of the substitution effect using the 2011 Great East Japan Earthquake, indicating that at least 40% of exports was substituted to other ports following the disaster. The substitution effect is the strongest in technology intensive product categories, which suggests an interaction between supply chains and domestic trade costs.