bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical evidence for the therapeutic value of TBX5 normalization in arrhythmia control
Authors: Rathjens Franziska S , Blenkle Alica , Iyer Lavanya M , Renger Anke , Syeda Fahima , Noack Claudia , Jungmann Andreas , Dewenter Matthias , Toischer Karl , El-Armouche Ali , Müller Oliver J , Fabritz Larissa , Zimmermann Wolfram-Hubertus , Zelarayan Laura C , Zafeiriou Maria-Patapia 
Published: August 2020

Abstract

Aims
Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mechanisms, we aimed to reveal the ventricular TBX5-dependent transcriptional network and further test the therapeutic potential of TBX5 level normalization in mice with documented arrhythmias.

Methods and results
We used a mouse model of TBX5 conditional deletion in ventricular cardiomyocytes. Ventricular (v) TBX5 loss in mice resulted in mild cardiac dysfunction and arrhythmias and was associated with a high mortality rate (60%) due to SCD. Upon angiotensin stimulation, vTbx5KO mice showed exacerbated cardiac remodelling and dysfunction suggesting a cardioprotective role of TBX5. RNA-sequencing of a ventricular-specific TBX5KO mouse and TBX5 chromatin immunoprecipitation was used to dissect TBX5 transcriptional network in cardiac ventricular tissue. Overall, we identified 47 transcripts expressed under the control of TBX5, which may have contributed to the fatal arrhythmias in vTbx5KO mice. These included transcripts encoding for proteins implicated in cardiac conduction and contraction (Gja1, Kcnj5, Kcng2, Cacna1g, Chrm2), in cytoskeleton organization (Fstl4, Pdlim4, Emilin2, Cmya5), and cardiac protection upon stress (Fhl2, Gpr22, Fgf16). Interestingly, after TBX5 loss and arrhythmia development in vTbx5KO mice, TBX5 protein-level normalization by systemic adeno-associated-virus (AAV) 9 application, re-established TBX5-dependent transcriptome. Consequently, cardiac dysfunction was ameliorated and the propensity of arrhythmia occurrence was reduced.

Conclusions
This study uncovers a novel cardioprotective role of TBX5 in the adult heart and provides preclinical evidence for the therapeutic value of TBX5 protein normalization in the control of arrhythmia.
Differences in Gut Bacterial Communities of Ips typographus (Coleoptera: Curculionidae) Induced by Enantiomer-Specific α-Pinene
Authors: Fang Jia-Xing , Zhang Su-Fang , Liu Fu , Zhang Xun , Zhang Feng-Bin , Guo Xiao-Bin , Zhang Zhen , Zhang Qing-He , Kong Xiang-Bo 
Published: August 2020

Abstract
The spruce bark beetle (Ips typographus L.) is a destructive pest of Eurasian spruce forests. Although the gut bacteria of this insect are considered to play important roles in its lifecycle, the relationship between I. typographus and its gut bacterial community is poorly characterized. In this study, 16S rRNA gene sequencing was used to determine gut bacterial community composition across successive I. typographus life stages. Responses of the gut bacteria to α-pinene enantiomers were also explored. Ips typographus gut bacterial populations were dominated by the phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, and the relative abundance of these phyla varied across different developmental stages of the beetle. Bacterial species diversity and richness indices increased with developmental stage progression. Relative abundances of the dominant genera, Erwinia (Enterobacteriales: Enterobacteriaceae), Pseudoxanthomonas (Xanthomonadales: Xanthomonadaceae), Serratia (Enterobacteriales: Enterobacteriaceae), and Romboutsia (Clostridiales: Peptostreptococcaceae), also varied across successive I. typographus life stages. Large disparities in the gut bacterial community of male adults were observed when the beetles were treated with S-(–)-α-pinene and R-(+)-α-pinene. The relative abundances of Lactococcus (Lactobacillales: Streptococcaceae) and Lelliottia (Enterobacteriales: Enterobacteriaceae) increased drastically with R-(+)-α-pinene and S-(–)-α-pinene treatment, respectively. This indicated a distinct enantiomer-specific effect of α-pinene on the I. typographus gut bacteria. This study demonstrated the plasticity of gut bacteria during I. typographus development, when α-pinene host monoterpenes are encountered. This study provides new insights into the relationship between ‘I. typographus–gut bacteria’ symbionts and host trees.
Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome: insights from stress echocardiography
Authors: Yakupoglu H Yakup , Saeed Sahrai , Senior Roxy , Baksi A John , Lyon Alexander R , Khattar Rajdeep S 
Published: August 2020

AbstractAims Takotsubo syndrome (TTS) is usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, a proportion of patients may have persistent symptoms. This study aimed to determine the haemodynamic and LV contractile responses to exercise in these patients.Methods and resultsThirty symptomatic TTS patients referred for exercise echocardiography, a median of 15 months following the index TTS episode, were matched with 30 controls with normal exercise echocardiography. Beta-blockers were withheld prior to the test. LV volumes, ejection fraction (EF) and wall motion score index (WMSI), were measured at rest and stress. The TTS cohort were Caucasian women with mean age of 64.6 ± 7.4 years and similar coronary risk factor profile and EF to controls. Resting systolic blood pressure (SBP), LV end-diastolic volume, wall stress, and right ventricular fractional area change were higher in TTS patients compared with controls. Stress echo data showed similar exercise time, peak heart rate, and peak SBP in TTS patients vs. controls, but TTS patients had higher LV volumes, lower exercise LVEF (70 ± 10% vs. 78 ± 7%; P = 0.001), ΔLVEF (4 ± 8% vs. 12 ± 5%; P &lt; 0.001), and WMSI (1.4 ± 0.4 vs. 1 ± 0; P &lt; 0.001) compared with controls. Twenty TTS patients had clear exercise-induced wall motion abnormalities, mainly involving the apex or more globally, with a mean ΔLVEF of 1% compared with 12% in controls. Among the other 10 TTS patients, the ΔLVEF was 10%.ConclusionSymptomatic patients with previous TTS have a blunted contractile response to exercise. The therapeutic and prognostic implications of these findings need further investigation.
Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)
Authors: Bouabdallaoui Nadia , Tardif Jean-Claude , Waters David D , Pinto Fausto J , Maggioni Aldo P , Diaz Rafael , Berry Colin , Koenig Wolfgang , Lopez-Sendon Jose , Gamra Habib , Kiwan Ghassan S , Blondeau Lucie , Orfanos Andreas , Ibrahim Reda , Grégoire Jean C , Dubé Marie-Pierre , Samuel Michelle , Morel Olivier , Lim Pascal , Bertrand Olivier F , Kouz Simon , Guertin Marie-Claude , L’Allier Philippe L , Roubille Francois 
Published: August 2020

Abstract

Aims
The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine.

Methods and results
In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (&lt;3, 4–7 and &gt;8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated &lt; Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or &gt; Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P &lt; 0.05).

Conclusion
Patients benefit from early, in-hospital initiation of colchicine after MI.

Trial Registration
COLCOT ClinicalTrials.gov number, NCT02551094.
Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry
Authors: DeFilippis Ersilia M , Collins Bradley L , Singh Avinainder , Biery David W , Fatima Amber , Qamar Arman , Berman Adam N , Gupta Ankur , Cawley Mary , Wood Malissa J , Klein Josh , Hainer Jon , Gulati Martha , Taqueti Viviany R , Di Carli Marcelo F , Nasir Khurram , Bhatt Deepak L , Blankstein Ron 
Published: August 2020

Abstract

Aims
There are sex differences in presentation, treatment, and outcomes of myocardial infarction (MI) but less is known about these differences in a younger patient population. The objective of this study was to investigate sex differences among individuals who experience their first MI at a young age.

Methods and results
Consecutive patients presenting to two large academic medical centres with a Type 1 MI at ≤50 years of age between 2000 and 2016 were included. Cause of death was adjudicated using electronic health records and death certificates. In total, 2097 individuals (404 female, 19%) had an MI (mean age 44 ± 5.1 years, 73% white). Risk factor profiles were similar between men and women, although women were more likely to have diabetes (23.7% vs. 18.9%, P = 0.028). Women were less likely to undergo invasive coronary angiography (93.5% vs. 96.7%, P = 0.003) and coronary revascularization (82.1% vs. 92.6%, P &lt; 0.001). Women were significantly more likely to have MI with non-obstructive coronary disease on angiography (10.2% vs. 4.2%, P &lt; 0.001). They were less likely to be discharged with aspirin (92.2% vs. 95.0%, P = 0.027), beta-blockers (86.6% vs. 90.3%, P = 0.033), angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (53.4% vs. 63.7%, P &lt; 0.001), and statins (82.4% vs. 88.4%, P &lt; 0.001). There was no significant difference in in-hospital mortality; however, women who survived to hospital discharge experienced a higher all-cause mortality rate (adjusted HR = 1.63, P = 0.01; median follow-up 11.2 years) with no significant difference in cardiovascular mortality (adjusted HR = 1.14, P = 0.61).

Conclusions
Women who experienced their first MI under the age of 50 were less likely to undergo coronary revascularization or be treated with guideline-directed medical therapies. Women who survived hospitalization experienced similar cardiovascular mortality with significantly higher all-cause mortality than men. A better understanding of the mechanisms underlying these differences is warranted.
Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study
Authors: Basso Cristina , Leone Ornella , Rizzo Stefania , De Gaspari Monica , van der Wal Allard C , Aubry Marie-Christine , Bois Melanie C , Lin Peter T , Maleszewski Joseph J , Stone James R 
Published: August 2020

Abstract

Aims
Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described.

Methods and results
In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.

Conclusions
In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases. Other forms of myocardial injury are also present in these patients. The macrophage infiltration may reflect underlying diseases rather than COVID-19.
Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk
Authors: Corpataux Noé , Spirito Alessandro , Gragnano Felice , Vaisnora Lukas , Galea Roberto , Svab Stefano , Gargiulo Giuseppe , Zanchin Thomas , Zanchin Christian , Siontis George C M , Praz Fabien , Lanz Jonas , Hunziker Lukas , Stortecky Stefan , Pilgrim Thomas , Räber Lorenz , Capodanno Davide , Urban Philip , Pocock Stuart , Heg Dik , Windecker Stephan , Valgimigli Marco 
Published: August 2020

Abstract

Aims
To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and &lt;4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria.

Methods and results
All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals.

Conclusion
All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.
Electrocardiographic features of 431 consecutive, critically ill COVID-19 patients: an insight into the mechanisms of cardiac involvement
Authors: Bertini Matteo , Ferrari Roberto , Guardigli Gabriele , Malagù Michele , Vitali Francesco , Zucchetti Ottavio , D’Aniello Emanuele , Volta Carlo Alberto , Cimaglia Paolo , Piovaccari Giancarlo , Corzani Alessandro , Galvani Marcello , Ortolani Paolo , Rubboli Andrea , Tortorici Gianfranco , Casella Gianni , Sassone Biagio , Navazio Alessandro , Rossi Luca , Aschieri Daniela , Rapezzi Claudio 
Published: August 2020

Abstract

Aims
Our aim was to describe the electrocardiographic features of critical COVID-19 patients.

Methods and results
We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value.

Conclusions
The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.
Creating healthy and active life for the elderly in programmes conducted by rural and urban-rural communes in Poland
Authors: Augustynowicz Anna , Waszkiewicz Michał , Szopa Sławomir , Borowska Mariola , Czerw Aleksandra 
Published: August 2020

Abstract

Background
In Poland, between 1989 and 2018 the number of the elderly increased by over 3.9 million. Demographic changes justify a senior policy focussed on the longest possible social, professional and family activity of the elderly. Directions of undertaken actions should include health policy programmes aimed at creating conditions healthy and active life of the elderly. The programmes should be particularly important in rural areas as the health of rural and urban residents differs. The study presents programmes for creating conditions for a healthy and active life of the elderly run by rural and urban-rural communes in 2012–17.

Methods
The study was conducted on the basis of existing data analysis. Data from the summary information prepared by voivodes and provided to the Minister of Health about implemented health policy programmes were used. Data on programmes concerning a healthy and active life for the elderly conducted by rural and urban-rural communes between 2012 and 2017 were extracted from the aggregate information.

Results
Between 2012 and 2017, 354 programmes were implemented, the most in 2016, and the least in 2015. There were 171 000 people participating in the programmes. The total cost was USD 2 491 664.

Conclusion
It can be presumed that in 2016 communes implemented more diagnostic and therapeutic programmes than in 2017. A small number of programmes and a small involvement of financial resources in communes with the largest number of the elderly may indicate marginalization of the importance of an active and healthy life for the elderly.
PbS biomineralization using cysteine: Bacillus cereus and the sulfur rush
Authors: Staicu Lucian C , Wojtowicz Paulina J , Pósfai Mihály , Pekker Péter , Gorecki Adrian , Jordan Fiona L , Barton Larry L 
Published: August 2020

Abstract
Bacillus sp. Abq, belonging to Bacillus cereus sensu lato, was isolated from an aquifer in New Mexico, USA and phylogenetically classified. The isolate possesses the unusual property of precipitating Pb(II) by using cysteine, which is degraded intracellularly to hydrogen sulfide (H2S). H2S is then exported to the extracellular environment to react with Pb(II), yielding PbS (galena). Biochemical and growth tests showed that other sulfur sources tested (sulfate, thiosulfate, and methionine) were not reduced to hydrogen sulfide. Using equimolar concentration of cysteine, 1 mM of soluble Pb(II) was removed from Lysogeny Broth (LB) medium within 120 h of aerobic incubation forming black, solid PbS, with a removal rate of 2.03 µg L−1 h−1 (∼8.7 µM L−1 h−1). The mineralogy of biogenic PbS was characterized and confirmed by XRD, HRTEM, and EDX. Electron microscopy and electron diffraction identified crystalline PbS nanoparticles with a diameter &lt;10 nm, localized in the extracellular matrix and on the surface of the cells. This is the first study demonstrating the use of cysteine in Pb(II) precipitation as insoluble PbS and it may pave the way to PbS recovery from secondary resources, such as Pb-laden industrial effluents.
Shotgun metagenomics of indigenous bacteria collected from the banks of the San Jacinto River for biodegradation of aromatic waste
Authors: Iyer Rupa , Damania Ashish 
Published: August 2020

ABSTRACT
Several Eastern Harris County communities lie near the now enclosed San Jacinto River (SJR) Waste Pit Superfund, a dumping ground for chlorinated dioxins and other paper mill waste products. Currently, no active monitoring of the SJR is conducted for these toxins with the exact concentration and health impact to the area unknown. As such, remediation and monitoring efforts outside of the Superfund itself could be necessary. To better understand the possible environmental fate of these aromatics, here we provide a shotgun metagenomic analysis of the structural and putative functional diversity of the SJR microbiome from two impacted Channelview, Texas communities bordering the Superfund. Results show that the underlying SJR microbiome possesses a core of metabolic enzymes related to the β-ketoadipate and benzoate degradation pathways. This suggests possible endpoints for many aromatics found deposited in the SJR including dioxin-like compounds. However, degradation biomarkers related to the priming and initial cleavage of chlorinated dioxin-like aromatics while present, are poorly concentrated across sampled sites. This may be due in part to decreased coverage of low abundance bacterial species, but also be a contributing factor leading to increased recalcitrance of these compounds in this environment compared to other aromatics.