bluuebunny/crossref_metadata_2025 huggingface dataset:
Unilateral branch pulmonary artery stenting in tetralogy of fallot improves ventricular function
Authors: Bissell MM , Mills L , Cave DGW , Foley R , Greenwood JP , Plein S , Thomson JDR , Bentham JR
Published: July 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIHR

Background

Pulmonary artery stenosis (PAS) occurs commonly in patients with tetralogy of fallot (ToF). Cardiac function and especially left ventricular longitudinal strain has been identified as an important prognostic factor for long term survival in ToF. The clinical relevance of unilateral PAS to long-term bi-ventricular function is poorly understood.

Purpose

We sought to evaluate the effect of resolving unilateral pulmonary artery obstruction on right and left ventricular performance.

Methods

We prospectively included 40 patients with TOF between 2016 and 2020, 20 who underwent unilateral PAS stenting and as comparison 20 who underwent surgical pulmonary valve replacement (PVR). MRI data was acquired during routine clinical care before and around 6-12 months after the procedure. 4 PAS patients attended additional research scans acquiring ventricular 4D flow MRI data. 4D flow MRI data was compared to the average kinetic energy curve of 10 age-matched healthy volunteers.

Results

Of the 20 patients undergoing PAS, 2 also underwent percutaneous PVR and were excluded from the comparison analysis. All patients in the PAs group showed an improvement in branch PA flow differential post procedure. Patients undergoing PAS were younger than those undergoing PVR (median 12 vs 19 years, p < 0.001). Other baseline anatomical and functional parameters including right ventricular (RV) volume indexed to body surface are (RVEDV/BSA) were comparable (pre PAS median 151 [122,170] vs pre PVR 162 [140,191]; p = 0.217). While in the PVR group the right ventricular volumes reduced in both end-diastole and end-systole, in the PAS group RV function improved due to reduced end-systolic volume with largely stable end-diastolic volumes.

Changes in the left ventricle (LV) were even more interesting. In the PVR group ejection fraction improved due to an increase in end-diastolic volume with no improvement in ventricular longitudinal strain. In contrast, in the PAS group LV ejection fraction improved by a reduction in end-systolic volume and the PAS group showed a small but significant improvement in LV longitudinal strain. In addition, ¾ patients undergoing 4D flow MRI assessment showed LV kinetic energy curve more similar to the healthy volunteer averaged  LV kinetic energy curve after PAS. The 4th patient already had a near normal LV kinetic energy curve prior to PAS.

Conclusion

Unilateral PAS does not alter RV end-diastolic volumes but improves RV function. LV ejection fraction improvement is similar to that seen after PVR, but importantly PAS also improved LV longitudinal strain. This suggests that PAS might positively influence long term morbidity and mortality risk in ToF patients, but a larger multi-centre long term follow-up study is needed to confirm this.
usefulness of the electrocardiogram and cardiac magnetic resonance to differentiate tachycardia induced cardiomyopathy from dilated cardiomyopathy in patients admitted for heart failure
Authors: Vera Sainz A , Cecconi A , Martinez-Vives P , Olivera MJ , Hernandez S , Tejelo J , Lopez Melgar B , Rojas Gonzalez A , Diez-Villanueva P , Salamanca J , Caballero P , Alfonso F , Jimenez-Borreguero LJ
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

In patients admitted for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and a concomitant high-rate supraventricular tachyarrhythmia (SVT) it is challenging to predict LVEF recovery after heart rate control and distinguish tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DC). The role of cardiac magnetic resonance (CMR) and the electrocardiogram (ECG) in this setting remains unsettled.

Methods

Forty-three consecutive patients admitted for HF due to high-rate SVT and LVEF <50% undergoing CMR in the acute phase were retrospectively included. Those who had LVEF >50% at follow up were classified as TIC and those with LVEF <50% were classified as DC. Clinical, laboratory, CMR and ECG findings were analyzed to predict LVEF recovery.

Results

Twenty-five (58%) patients were classified as TIC. Patients with DC had wider QRS (121.2 ± 26 vs 97.7 ± 17.35 ms; p = 0.003). On CRM the TIC group presented with higher LVEF (33.4 ± 11 vs 26.9 ± 6.4% p = 0.019) whereas late gadolinium enhancement (LGE) was more frequent in DC group (61 vs 16% p = 0.004). On multivariate analysis, QRS duration ≥100 ms (p = 0.027), LVEF < 40% on CMR (p = 0.047) and presence of LGE (p = 0.03) were identified as independent predictors of lack of LVEF recovery. Furthermore, during clinical follow-up (median 60 months) DC patients were admitted more frequently for HF (44% vs 0%; p < 0.001) than TIC patients (Figure 1).

Conclusion

In patients with reduced LVEF admitted for HF due to high-rate SVT, QRS duration ≥100 ms, LVEF <40% on CMR and presence of LGE are independently associated with lack of LVEF recovery and worse clinical outcome.
Sex and age differences in patients with a working diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA): presentation and outcome
Authors: Williams MGL , Dastidar A , Liang K , Johnson TW , Baritussio A , Strange JW , Joshi N , Dorman S , Dr Garate E , Spagnoli L , Fiori E , Lawton CB , Biglino G , Plein S , Bucciarelli-Ducci C
Published: July 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Rosetrees Trust James Tudor Foundation

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is an increasingly recognised working diagnosis. Sex and age differences in MINOCA are not well understood.

Purpose  This study aims to evaluate the impact of sex and age in patients with MINOCA due to ischaemic and non-ischaemic causes on clinical presentation and outcome.

Methods and Results Consecutive patients with a working diagnosis of MINOCA (n = 719) from a single tertiary centre who underwent comprehensive cardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) were followed prospectively. The primary endpoint was all-cause mortality.  CMR was performed at a median time of 30 days after presentation and identified a diagnosis in 74% of patients. Men were more likely to have a non-ischaemic cause on CMR (55% v. 41%, p < 0.001) and less likely to have a normal/non-specific scan (21% v. 32%, p = 0.001, figure 1).  All-cause mortality was 9.5% over a median follow up of 4.9 years, with no significant difference between sexes (8.7% versus 10.1% p = 0.456).  Age group (HR 1.61, p < 0.001) and LVEF (HR 0.98, p = 0.020) were independent predictors of mortality. Men aged >60 years with a non-ischaemic aetiology on their CMR were at higher risk of death than women with non-ischaemic causes >60 years (p = 0.003, figure 2).

Conclusions There is no difference in all-cause mortality between sexes in MINOCA but increasing age is the most important predictor of mortality in both sexes.
Impact of concomitant impairments of the left and right ventricular myocardial strain on the prognoses of patients with ST-elevation myocardial infarction
Authors: Wei LAI , Ge HENG , Pu JUN
Published: July 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China

OnBehalf

Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University

Background

 The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear.

Methods

 We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12h and CMR examination within 1 week (median,5 days; range, 2-7 days) after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke.

Results

During follow-up (median: 52 months, interquartile range: 29–78 months), 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > -11.20% was an independent predictor of MACCEs (P < 0.001). The impairment of RV strain was found in 177 patients (42.14%), including 37.8% of patients with left anterior descending occlusions, 37.5% with left circumflex occlusions, and 51.5% with right coronary artery occlusions. Although none of the three individual RV strain measurements, the RV-GLS, RV-GRC and RV-GCS, was independently associated with the risk of MACCEs, patients who had RV-GRS ≤ 38.79% in addition to an impaired LV-GCS however were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank P = 0.010). Moreover, the addition of RV-GRS to LV-GCS improved the predictive power for MACCEs compared to the predictive power of LV-GCS alone (continuous NRI: 0.327; 95% CI: 0.095 - 0.558; P = 0.006). Finally, Tobacco use (P = 0.003), right coronary artery involvement (P = 0.002), and LV-GCS > -11.20% (P = 0.012) were found to be independent risk factors of RV-GRS impairment.

Conclusions

 Impairment of the RV strain is prevalent in infarctions occurring at all cardiac locations. While LV-GCS is an independent predictor of long-term MACCEs, the concomitant impairment of RV-GRS results in a worsened prognosis. Combination assessment of both LV and RV strain indexes could improve risk stratification of STEMI patients.
Could we use cardiac MRIfor diagnosis of infective endocarditis
Authors: Elagha AE , Beniamin YB , El-Aroussy WE , Meshaal MM
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Echocardiography is a reliable imaging tool in diagnosing infective endocarditis (IE) according to "modified Dukes criteria"; however, it lacks tissue characterization of cardiac masses, and transthoracic echocardiography (TTE) has low sensitivity in detection of vegetations. Moreover, transesophageal echo (TEE) is considered semi-invasive and intolerable in some situations .On the other hand, cardiac magnetic resonance (CMR) is a powerful true 3D imaging tool with wide field of view, and superior capability of tissue characterization of cardiac masses; however, modest information is available about utility of CMR in diagnosing IE.

Purpose

To assess the feasibility of CMR to identify vegetations and complications of IE, and compare obtained findings with those obtained from echocardiography regarding: presence, number, size of vegetations, and detection of cardiac complications (e.g. aortic root abscess, periannular abscess, and shunts).

Materials and Methods

Eighty consecutive patients with suspected IE were enrolled in the study. All patients underwent TTE; only those with left-sided lesions underwent TEE.  When clinical situation allowed, CMR examination using 1.5 Tesla magnet were performed using the following sequences: Steady-state free precession (SSFP), T1W (± fat suppression) and T2W, first-pass perfusion, and delayed hyperenhancement. Moreover, chest and abdominal survey was done.

Results

Sixty-one patients (45 males and 16 females) were able to undergo and complete CMR study. Affection of tricuspid valve was seen in 39.3%, mitral 31.1%, aortic 24.6%, and pulmonary 4.9% of cases. All vegetations visualized by echocardiography were also clearly detected and confirmed by CMR. The sensitivity, specificity, accuracy and Kappa agreement of CMR with echocardiography in depicting >0.5cm vegetations were all 100%. By tissue characterization, vegetations resemble features of thrombi (with variation in signal intensity according to age of vegetation). However, in some cases, masses have a unique pattern that is different from vegetations of IE, and subsequently other diagnoses were suggested (e.g. fibroelastoma, Libman-Saks endocarditis). In 22 patients, CMR provided more information than echocardiography, and in 6 patients, CMR made a paradigm shift of diagnosis.

Conclusion

Cardiac MRI is a powerful imaging tool in diagnosis of IE and its complications. In comparison with echocardiography, CMR can identify the presence, numbers, and size of vegetations accurately. Moreover, with its unique ability of tissue characterization, CMR helps distinguish vegetations from other masses; therefore changes the diagnosis of IE and subsequent management in some patients.
Wall shear stress angle determines aortic growth in patients with bicuspid aortic valves
Authors: Minderhoud SCS , Roos-Hesselink JW , Chelu RG , Bons LR , Van Den Hoven AT , Korteland SA , Van Den Bosch AE , Budde RPJ , Wentzel JJ , Hirsch A
Published: July 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Dutch Heart Foundation

Background

Patients with bicuspid aortic valve (BAV) have altered flow velocity patterns with different wall shear stress (WSS) distributions in the ascending aorta compared to patients with tricuspid aortic valves. These WSS distributions are associated with aortic dilatation in cross sectional studies, however, longitudinal data demonstrating a potential causative role is missing.

Purpose

The aim of this study was to assess the differences in WSS distributions between BAV patients and healthy subjects and to determine the predictive value of WSS for aortic growth in patients with a BAV.

Methods

Forty patients with a BAV and 32 healthy matched subjects were prospectively studied by 4D-flow cardiovascular magnetic resonance (CMR). Peak velocity, pulse wave velocity, aortic distensibility, peak systolic WSS (magnitude), the different WSS components (axial and circumferential), and WSS angle were assessed in the proximal ascending aorta. WSS angle was defined as the angle between the WSSmagnitude and WSSaxial component. In the BAV patients, aortic volumetric growth over three years was determined in the proximal ascending aorta (first 5cm) based on CT angiography. Multivariate linear regression analysis was used to identify independent predictors of aortic volumetric growth.

Results

Of the BAV patients, 21 (53%) had a left-right fusion pattern and eight patients had Turner syndrome. WSSaxial was significantly lower in BAV patients compared to healthy subjects (p = 0.008) and WSScircumferential and WSS angle were significantly higher (both p < 0.001, see Figure). WSSmagnitude, pulse wave velocity, and aorta distensibility were not statistically significant different. WSSmagnitude (0.69 N/m² [0.51-0.81] vs 1.08 N/m² [0.89-1.24], p = 0.005), WSSaxial (0.50 N/m² [0.39-0.61] vs 0.72 N/m²  [0.54-0.94], p = 0.015) and WSScircumferential (0.34 N/m² [0.32-0.46] vs 0.64 N/m² [0.47-0.81], p = 0.008) were significantly lower in BAV Turner patients compared to BAV non-Turner patients, while WSS angle (40° [34-41] vs 40° [32-48], p = 0.607) was not statistically significant different. During a follow-up of three years, there was a significant growth of the proximal ascending aorta in the BAV patients (1.2 cm3 [-0.2-2.5], p = 0.001). In multivariate analysis corrected for baseline aortic volume and diastolic blood pressure, WSS angle was the only independent predictor for proximal aortic volume growth (β=0.108, p = 0.030).

Conclusions

Increased WSScircumferential and especially WSS angle are present in patients with BAV. WSS angle was the only independent predictor of aortic growth. These findings highlight the potential role of  WSS measurements in patients with BAV to stratify patients at risk for aortic dilation.
Cardio-renal benefits of sodium–glucose co-transporter 2 inhibitors in heart failure with reduced ejection fraction: mechanisms and clinical evidence
Authors: Aguilar-Gallardo Jose S , Correa Ashish , Contreras Johanna P
Published: July 2021

The heart and the kidneys are closely interconnected, and disease in one organ system can lead to disease in the other. This interdependence is illustrated in heart failure with reduced ejection fraction (HFrEF), where worsening heart failure (HF) can lead to renal dysfunction and vice versa. Further complicating this situation is the fact that drugs that serve as guideline-directed medical therapy for HFrEF can affect renal function. Sodium–glucose co-transporter 2 (SGLT2) inhibitors are a new class of medication with an evolving role in HF and chronic kidney disease (CKD). Initially found to have benefits in diabetic patients, new research established potential cardiovascular and renal benefits in patients with HF independent of their diabetic status and in populations with CKD. This has been established by landmark trials such as EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), EMPA-TROPISM (Are the ‘Cardiac Benefits’ of Empagliflozin Independent of Its Hypoglycemic Activity), CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation), DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease), DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), and DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms and Functional Status in Patients with HF with Reduced Ejection Fraction). Multiple mechanisms responsible for these benefits have been suggested by clinical and non-clinical studies, and involve cardiac and renal energetic efficiency, cardiac remodelling, preservation of renal function, immunomodulation, changes in haematocrit, and control of risk factors. As such, SGLT2 inhibitors have tremendous potential to improve outcomes in populations with HF and CKD. The purpose of this review is to discuss the current evidence and underlying mechanisms for the cardio-renal benefits of SGLT2 inhibitors in patients with HFrEF.
Comprehensive analysis of haemodynamics in patients with physiologically curved prostheses of the ascending aorta
Authors: Sieren Malte Maria , Balks Maren Friederike , Schlueter Jennifer Kristina , Wegner Franz , Huellebrand Markus , Scharfschwerdt Michael , Barkhausen Jörg , Frydrychowicz Alex , Gabbert Dominik Daniel , Oechtering Thekla Helene
Published: July 2021

OBJECTIVES

This is a comprehensive analysis of haemodynamics after valve-sparing aortic root replacement (VSARR) with anatomically curved prosthesis (CP) compared to straight prosthesis (SP) and age-matched volunteers (VOL) using 4D flow MRI (time-resolved three-dimensional magnetic resonance phase-contrast imaging).

METHODS

Nine patients with 90° CP, nine patients with SP, and twelve VOL were examined with 4D flow MRI. Analyses included various characteristic anatomical, qualitative and quantitative haemodynamic parameters.

RESULTS

Grading of secondary flow patterns was lower in CP patients than in SP patients (P = 0.09) and more comparable to VOL, albeit not reaching statistical significance. However, it was easy to differentiate between VSARR patients and healthy volunteers: Patients more often had angular aortic arches (CP: 89%, SP: 100%; VOL: 17%; P ≤ 0.002), increased average curvature (CP: 0.17/cm [0.15, 0.18]; SP: 0.15/cm [0.14, 0.16]; VOL: 0.14/cm [0.13, 0.16]; P ≤ 0.007; values given as median [interquartile range]), and more secondary flow patterns (CP: 3 [2, 4] SP: 3 [2, 3] VOL: 2 [1, 2]; P < 0.01). Maximum circulation (CP: 142.7 cm2/s [116.1, 187.3]; SP: 101.8 cm2/s [77.7, 132.5]; VOL: 42.8cm2/s [39.3, 65.6]; P ≤ 0.002), maximum helicity density (CP: 9.6 m/s2 [9.3, 23.9]; SP: 9.7 m/s2 [8.6, 12.5]; VOL 4.9 m/s2 [4.2, 7.7]; P ≤ 0.007), and wall shear stress gradient (e.g., proximal ascending aorta CP: 0.97 N/m2 [0.54, 1.07]; SP: 1.08 N/m2 [0.74, 1.24]; VOL: 0.41 N/m2 [0.32, 0.60]; P ≤ 0.01) were increased in patients. One CP patient had a round aortic arch with physiological haemodynamic parameters.

CONCLUSIONS

The restoration of physiological aortic configuration and haemodynamics was not fully achieved with the curved prostheses in our study cohort. However, there was a tendency towards improved haemodynamic conditions in the patients with curved prostheses overall but without statistical significance. A single patient with a CP and near-physiological configuration of the thoracic aorta underlines the importance of optimizing postoperative geometric conditions for allowing for physiological haemodynamics and cardiovascular energetics after VSARR.
Autotuning Hamiltonian Monte Carlo for efficient generalized nullspace exploration
Authors: Fichtner Andreas , Zunino Andrea , Gebraad Lars , Boehm Christian
Published: July 2021

We propose methods to efficiently explore the generalized nullspace of (non-linear) inverse problems, defined as the set of plausible models that explain observations within some misfit tolerance. Owing to the random nature of observational errors, the generalized nullspace is an inherently probabilistic entity, described by a joint probability density of tolerance values and model parameters. Our exploration methods rest on the construction of artificial Hamiltonian systems, where models are treated as high-dimensional particles moving along a trajectory through model space. In the special case where the distribution of misfit tolerances is Gaussian, the methods are identical to standard Hamiltonian Monte Carlo, revealing that its apparently meaningless momentum variable plays the intuitive role of a directional tolerance. Its direction points from the current towards a new acceptable model, and its magnitude is the corresponding misfit increase. We address the fundamental problem of producing independent plausible models within a high-dimensional generalized nullspace by autotuning the mass matrix of the Hamiltonian system. The approach rests on a factorized and sequentially preconditioned version of the L-BFGS method, which produces local Hessian approximations for use as a near-optimal mass matrix. An adaptive time stepping algorithm for the numerical solution of Hamilton’s equations ensures both stability and reasonable acceptance rates of the generalized nullspace sampler. In addition to the basic method, we propose variations of it, where autotuning focuses either on the diagonal elements of the mass matrix or on the macroscopic (long-range) properties of the generalized nullspace distribution. We quantify the performance of our methods in a series of numerical experiments, involving analytical, high-dimensional, multimodal test functions. These are designed to mimic realistic inverse problems, where sensitivity to different model parameters varies widely, and where parameters tend to be correlated. The tests indicate that the effective sample size may increase by orders of magnitude when autotuning is used. Finally, we present a proof of principle of generalized nullspace exploration in viscoelastic full-waveform inversion. In this context, we demonstrate (1) the quantification of inter- and intraparameter trade-offs, (2) the flexibility to change model parametrization a posteriori, for instance, to adapt averaging length scales, (3) the ability to perform dehomogenization to retrieve plausible subwavelength models and (4) the extraction of a manageable number of alternative models, potentially located in distinct local minima of the misfit functional.
Is fertility reduced in ovulatory women with polycystic ovary syndrome? An opinion paper
Authors: Palomba Stefano
Published: July 2021

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility; however, whether women with PCOS and spontaneous or drug-induced ovulatory cycles have the same reproductive potential as non-PCOS controls is a matter of debate. In the present opinion paper, the author takes the opportunity to summarize the collective evidence supporting the hypothesis of reduced fertility potential in women with PCOS, regardless of ovulatory status, and speculate that reduced reproductive potential may be caused by altered oocytes, embryo and endometrial competence, and infertility-related co-morbidities as well as an increased risk of pregnancy complications.
Elimination of CO2 insufflation-induced hypercapnia in open heart surgery using an additional venous reservoir
Authors: Nyman Jesper , Holm Manne , Fux Thomas , Sesartic Vanja , Fredby Magnus , Svenarud Peter , van der Linden Jan
Published: July 2021

OBJECTIVES

Carbon dioxide (CO2) gas insufflation is used for continuous de-airing during open heart surgery. The aim was to evaluate if an additional separate venous reservoir eliminates CO2 insufflation-induced hypercapnia and keeps sweep gas flow of the oxygenator constant.

METHODS

A separate reservoir was used during cardiopulmonary bypass in addition to a standard venous reservoir. The additional reservoir received drained blood and CO2 gas continuously via a suction drain (1 l/min) and handheld suction devices from the surgical wound. CO2 gas was insufflated via a gas diffuser in the open wound at 10 l/min. In a cross-over design for each patient, gas and blood were either continuously drained from the additional to the standard venous reservoir or not. CO2 pressure in arterial blood (PaCO2) was measured after adjustment of sweep gas flow as necessary and after steady state of PaCO2 was observed. Mean values for each setup (median 4 times) for each patient were analysed with Wilcoxon rank-sum test.

RESULTS

Ten adult patients undergoing open aortic valve replacement were included. Median PaCO2 did not differ between setups (5.41; 5.29–5.57, interquartile range vs 5.41; 5.24–5.58, P = 0.92), whereas sweep gas flow (l/min) was lower (2.58; 2.50–3.16 vs 4.42; 4.0–5.40, P = 0.002) when CO2 gas was not drained from the additional to the standard reservoir.

CONCLUSIONS

An additional venous reservoir for the evacuation of blood from the open surgical wound eliminates CO2 insufflation-induced hypercapnia in open heart surgery keeping PaCO2 and sweep gas flow constant. This prevents possible CO2-induced hyperperfusion of the brain and decreases the risk of cerebral particulate embolization during CO2 insufflation for de-airing in open heart surgery.

Clinical trial registration

NCT04202575.

IRB approval dat and number

2018-07-13 and 2018/1091-31.
Identification and characteristics of a novel aminoglycoside phosphotransferase, APH(3′)-IId, from an MDR clinical isolate of Brucella intermedia
Authors: Lu Wei , Li Kewei , Huang Jiansheng , Sun Zhewei , Li Aifang , Liu Hongmao , Zhou Danying , Lin Hailong , Zhang Xueya , Li Qiaoling , Lu Junwan , Lin Xi , Li Peizhen , Zhang Hailin , Xu Teng , Bao Qiyu
Published: July 2021

Objectives

To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3′)-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient.

Methods

Species identity was determined by PCR and MALDI-TOF MS analysis. WGS was performed to determine the genetic elements conferring antimicrobial resistance. Gene cloning, transcriptional analysis and targeted gene deletion, as well as protein purification and kinetic analysis, were performed to investigate the mechanism of resistance.

Results

APH(3′)-IId consists of 266 amino acids and shares the highest identity (48.25%) with the previously known APH(3′)-IIb. Expression of aph(3′)-IId in Escherichia coli decreased susceptibility to kanamycin, neomycin, paromomycin and ribostamycin. The aph(3′)-IId gene in ZJ499 was transcriptionally active under laboratory conditions and the relative abundance of this transcript was unaffected by treatment with the above four antibiotics. However, deletion of aph(3′)-IId in ZJ499 results in decreased MICs of these drugs. The purified APH(3′)-IId showed phosphotransferase activity against kanamycin, neomycin, paromomycin and ribostamycin, with catalytic efficiencies (kcat/Km) ranging from ∼105 to 107 M−1 s−1. Genetic environment and comparative genomic analyses suggested that aph(3′)-IId is probably a ubiquitous gene in Brucella, with no mobile genetic elements detected in its surrounding region.

Conclusions

APH(3′)-IId is a novel chromosomal aminoglycoside phosphotransferase and plays an important role in the resistance of B. intermedia ZJ499 to kanamycin, neomycin, paromomycin and ribostamycin. To the best of our knowledge, APH(3′)-IId represents the fourth characterized example of an APH(3′)-II enzyme.
Data-driven identification of temporal glucose patterns in a large cohort of nondiabetic patients with COVID-19 using time-series clustering
Authors: Mistry Sejal , Gouripeddi Ramkiran , Facelli Julio C
Published: July 2021

Objective

Hyperglycemia has emerged as an important clinical manifestation of coronavirus disease 2019 (COVID-19) in diabetic and nondiabetic patients. Whether these glycemic changes are specific to a subgroup of patients and persist following COVID-19 resolution remains to be elucidated. This work aimed to characterize longitudinal random blood glucose in a large cohort of nondiabetic patients diagnosed with COVID-19.

Materials and Methods

De-identified electronic medical records of 7502 patients diagnosed with COVID-19 without prior diagnosis of diabetes between January 1, 2020, and November 18, 2020, were accessed through the TriNetX Research Network. Glucose measurements, diagnostic codes, medication codes, laboratory values, vital signs, and demographics were extracted before, during, and after COVID-19 diagnosis. Unsupervised time-series clustering algorithms were trained to identify distinct clusters of glucose trajectories. Cluster associations were tested for demographic variables, COVID-19 severity, glucose-altering medications, glucose values, and new-onset diabetes diagnoses.

Results

Time-series clustering identified a low-complexity model with 3 clusters and a high-complexity model with 19 clusters as the best-performing models. In both models, cluster membership differed significantly by death status, COVID-19 severity, and glucose levels. Clusters membership in the 19 cluster model also differed significantly by age, sex, and new-onset diabetes mellitus.

Discussion and Conclusion

This work identified distinct longitudinal blood glucose changes associated with subclinical glucose dysfunction in the low-complexity model and increased new-onset diabetes incidence in the high-complexity model. Together, these findings highlight the utility of data-driven techniques to elucidate longitudinal glycemic dysfunction in patients with COVID-19 and provide clinical evidence for further evaluation of the role of COVID-19 in diabetes pathogenesis.
Urinary Thromboxane B2 and Lethal Prostate Cancer in African American Men
Authors: Kiely Maeve , Milne Ginger L , Minas Tsion Z , Dorsey Tiffany H , Tang Wei , Smith Cheryl J , Baker Francine , Loffredo Christopher A , Yates Clayton , Cook Michael B , Ambs Stefan
Published: July 2021

Background

Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. We investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men.

Methods

We measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, with mass spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of TXB2 with prostate cancer and patient survival. The median survival follow-up was 8.4 years, with 246 deaths among cases. Aspirin use was assessed with a questionnaire. Race was self-reported.

Results

Urinary TXB2 was inversely associated with aspirin use. High (>median) TXB2 was associated with prostate cancer in AA (adjusted odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.13 to 2.00) but not EA men (OR = 1.07, 95% CI = 0.82 to 1.40), suggesting upregulated TXA2 synthesis in AA men with prostate cancer. High TXB2 was positively associated with metastatic prostate cancer (OR = 2.60, 95% CI = 1.08 to 6.28) compared with low (≤median) TXB2. Furthermore, high TXB2 was also associated with all-cause (adjusted hazard ratio = 1.59, 95% CI = 1.06 to 2.40) and prostate cancer-specific mortality (hazard ratio = 4.74, 95% CI = 1.62 to 13.88) in AA men only.

Conclusions

We report a distinct association of TXB2 with prostate cancer outcomes in AA men. In this high-risk group of men, upregulation of TXA2 synthesis may promote metastasis and lethal disease. Our observation identifies a potential benefit of aspirin in preventing lethal prostate cancer through inhibition of TXA2 synthesis.
Smoking and Incidence of Colorectal Cancer Subclassified by Tumor-Associated Macrophage Infiltrates
Authors: Ugai Tomotaka , Väyrynen Juha P , Haruki Koichiro , Akimoto Naohiko , Lau Mai Chan , Zhong Rong , Kishikawa Junko , Väyrynen Sara A , Zhao Melissa , Fujiyoshi Kenji , Dias Costa Andressa , Borowsky Jennifer , Arima Kota , Guerriero Jennifer L , Fuchs Charles S , Zhang Xuehong , Song Mingyang , Wang Molin , Giannakis Marios , Meyerhardt Jeffrey A , Nowak Jonathan A , Ogino Shuji
Published: July 2021

Background

Biological evidence indicates that smoking can influence macrophage functions and polarization, thereby promoting tumor evolution. We hypothesized that the association of smoking with colorectal cancer incidence might differ by macrophage infiltrates.

Methods

Using the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association of smoking with incidence of colorectal cancer subclassified by macrophage counts. Multiplexed immunofluorescence (for CD68, CD86, IRF5, MAF, and MRC1 [CD206]) combined with digital image analysis and machine learning was used to identify overall, M1-polarized, and M2-polarized macrophages in tumor. We used inverse-probability–weighted multivariable Cox proportional hazards regression models to control for potential confounders and selection bias because of tissue data availability. All statistical tests were 2-sided.

Results

During follow-up of 131 144 participants (3 648 370 person-years), we documented 3092 incident colorectal cancer cases, including 871 cases with available macrophage data. The association of pack-years smoked with colorectal cancer incidence differed by stromal macrophage densities (Pheterogeneity = .003). Compared with never smoking, multivariable-adjusted hazard ratios (95% confidence interval) for tumors with low macrophage densities were 1.32 (0.97 to 1.79) for 1-19 pack-years, 1.31 (0.92 to 1.85) for 20-39 pack-years, and 1.74 (1.26 to 2.41) for 40 or more pack-years (Ptrend = .004). In contrast, pack-years smoked was not statistically significantly associated with the incidence of tumors having intermediate or high macrophage densities (Ptrend > .009, with an α level of .005). No statistically significant differential association was found for colorectal cancer subclassified by M1-like or M2-like macrophages.

Conclusions

The association of smoking with colorectal cancer incidence is stronger for tumors with lower stromal macrophage counts. Our findings suggest an interplay of smoking and macrophages in colorectal carcinogenesis.
A small cog in a large wheel: crucial role of miRNAs in root apical meristem patterning
Authors: Bertolotti Gaia , Scintu Daria , Dello Ioio Raffaele
Published: July 2021

In both animal and plants, establishment of body axes is fundamental for proper organ development. Plant roots show two main developmental axes: the proximo-distal axis, which spans from the hypocotyl–root junction to the root tip; and the radial axis, which traverses from the vascular tissue to the epidermis. Root axes are determined in the root meristem. The root meristem occupies the tip of the root and contains self-renewing stem cells, which continuously produce new root cells. An intricate network of signalling pathways regulates meristem function and patterning to ensure proper root development and growth. In the last decade, miRNAs, 20–21 nucleotide-long molecules with morphogenetic activity, emerged as central regulators of root cell patterning. Their activity intersects with master regulators of meristematic activity, including phytohormones. In this review, we discuss the latest findings about the activity of miRNAs and their interaction with other molecular networks in the formation of root meristem axes. Furthermore, we describe how these small molecules allow root growth to adapt to changes in the environment, while maintaining the correct patterning.
Antifungal susceptibility of clinical Cryptococcus gattii isolates from Colombia varies among molecular types
Authors: Firacative Carolina , Escandón Patricia
Published: July 2021

Cryptococcosis by Cryptococcus gattii is endemic in Colombia, affecting mostly immunocompetent hosts. Since antifungal susceptibility differs between molecular types of cryptococcal isolates, as reported elsewhere, the aim of this study was to determine if 42 Colombian clinical isolates, VGI, VGII and VGIII, differ in the susceptibility to commonly used antifungals, using Sensititre plates. Among the molecular types, six non-wild type isolates to fluconazole, voriconazole, and 5-flucytosine, were identified. Besides, VGI and VGII were less susceptible to 5-flucytosine and azoles, respectively, than other molecular types. These findings support the applicability of practicing susceptibility testing, which could better guide treatment in cryptococcosis.

Lay Summary

Cryptococcosis gattii affects immunocompetent people. For a correct treatment, antifungal susceptibility testing is essential. This study shows differences in the susceptibility to commonly used antimycotics among genotypes of Colombian clinical C. gattii isolates, some of which are non-wild-type.
Evolution of the galaxy stellar mass function: evidence for an increasing M* from z = 2 to the present day
Authors: Adams N J , Bowler R A A , Jarvis M J , Häußler B , Lagos C D P
Published: July 2021

Utilizing optical and near-infrared broad-band photometry covering >5 deg2 in two of the most well-studied extragalactic legacy fields (COSMOS and XMM-LSS), we measure the galaxy stellar mass function (GSMF) between 0.1 < z < 2.0. We explore in detail the effect of two source extraction methods (SExtractor and ProFound) in addition to the inclusion/exclusion of Spitzer IRAC 3.6 and 4.5 μm photometry when measuring the GSMF. We find that including IRAC data reduces the number of massive (log10(M/M⊙) > 11.25) galaxies found due to improved photometric redshift accuracy, but has little effect on the more numerous lower-mass galaxies. We fit the resultant GSMFs with double Schechter functions down to log10(M/M⊙) = 7.75 (9.75) at z = 0.1 (2.0) and find that the choice of source extraction software has no significant effect on the derived best-fitting parameters. However, the choice of methodology used to correct for the Eddington bias has a larger impact on the high-mass end of the GSMF, which can partly explain the spread in derived M* values from previous studies. Using an empirical correction to model the intrinsic GSMF, we find evidence for an evolving characteristic stellar mass with δlog10(M*/M⊙)/δz = $-0.16\pm 0.05 \, (-0.11\pm 0.05)$, when using SExtractor (ProFound). We argue that with widely quenched star formation rates in massive galaxies at low redshift (z < 0.5), additional growth via mergers is required in order to sustain such an evolution to a higher characteristic mass.
A new radio census of neutron star X-ray binaries
Authors: van den Eijnden J , Degenaar N , Russell T D , Wijnands R , Bahramian A , Miller-Jones J C A , Hernández Santisteban J V , Gallo E , Atri P , Plotkin R M , Maccarone T J , Sivakoff G , Miller J M , Reynolds M , Russell D M , Maitra D , Heinke C O , Armas Padilla M , Shaw A W
Published: July 2021

We report new radio observations of a sample of 36 neutron star (NS) X-ray binaries, more than doubling the sample in the literature observed at current-day sensitivities. These sources include 13 weakly magnetized (B < 1010 G) and 23 strongly magnetized (B ≥ 1010 G) NSs. 16 of the latter category reside in high-mass X-ray binaries, of which only two systems were radio-detected previously. We detect four weakly and nine strongly magnetized NSs; the latter are systematically radio fainter than the former and do not exceed LR ≈ 3 × 1028 erg s−1. In turn, we confirm the earlier finding that the weakly magnetized NSs are typically radio fainter than accreting stellar-mass black holes. While an unambiguous identification of the origin of radio emission in high-mass X-ray binaries is challenging, we find that in all but two detected sources (Vela X-1 and 4U 1700-37) the radio emission appears more likely attributable to a jet than the donor star wind. The strongly magnetized NS sample does not reveal a global correlation between X-ray and radio luminosity, which may be a result of sensitivity limits. Furthermore, we discuss the effect of NS spin and magnetic field on radio luminosity and jet power in our sample. No current model can account for all observed properties, necessitating the development and refinement of NS jet models to include magnetic field strengths up to 1013 G. Finally, we discuss jet quenching in soft states of NS low-mass X-ray binaries, the radio non-detections of all observed very-faint X-ray binaries in our sample, and future radio campaigns of accreting NSs.
A consistent and robust measurement of the thermal state of the IGM at 2 ≤ z ≤ 4 from a large sample of  Ly α forest spectra: evidence for late and rapid He ii reionization
Authors: Gaikwad Prakash , Srianand Raghunathan , Haehnelt Martin G , Choudhury Tirthankar Roy
Published: July 2021

We characterize the thermal state of the intergalactic medium (IGM) in 10 redshift bins in the range 2 ≤ z ≤ 4 with a sample of 103 high-resolution, high S/N  Ly α forest spectra using four different flux distribution statistics. Our measurements are calibrated with mock spectra from a large suite of hydrodynamical simulations post-processed with our thermal IGM evolution code cite, finely sampling amplitude, and slope of the expected temperature–density relation. The thermal parameters inferred from our measurements of the flux power spectrum, Doppler parameter distribution, as well as wavelet and curvature statistics agree well within their respective errors and all clearly show the peak in temperature and minimum in slope of the temperature density relation expected from  He ii reionization. Combining our measurements from the different flux statistics gives T0 = (14 750 ± 1322) K for the peak temperature at mean density and a corresponding minimum slope γ = 1.225 ± 0.120. The peak in the temperature evolution occurs around z ≈ 3, in agreement with previous measurements that had suggested the presence of such a peak, albeit with a large scatter. Using cite, we also calculate the thermal state of the IGM predicted by five widely used (spatially homogeneous) UV-background models. The rather rapid thermal evolution inferred by our measurements is well reproduced by two of the models, if we assume (physically well motivated) non-equilibrium evolution with photoheating rates that are reduced by a moderate factor of ∼0.7–0.8. The other three models predict  He ii reionization to be more extended with a higher temperature peak occurring somewhat earlier than our measurements suggest.
Asteroseismic analysis of eight solar-like oscillating evolved stars in the open cluster NGC 6811
Authors: Çelik Orhan Zeynep
Published: July 2021

The Kepler space telescope has provided exquisite data with which to perform asteroseismic analysis on evolved star ensembles. Studying star clusters offers significant insight into stellar evolution and structure, due to having a large number of stars with essentially the same age, distance, and chemical composition. This study analysed eight solar-like oscillating evolved stars that are members of the open cluster NGC 6811 and modelled them for the first time. The fundamental stellar parameters are obtained from the interior model using observational asteroseismic and non-asteroseismic constraints. The stellar interior models are constructed using the mesa evolution code. The mass-loss method is included in the interior models of the stars. The stellar masses and radius ranges of the stars are 2.23–2.40 M⊙ and 8.47–12.38 R⊙, respectively. Typical uncertainties for the mass and radius are ∼0.11 M⊙ and ∼0.09 R⊙, respectively. The model masses and radii are compared with masses and radii obtained from asteroseismic and non-asteroseismic methods (scaling relations and classic methods). The stellar ages fell in the range between 0.71 and 0.82 Gyr, with a typical uncertainty of ${\sim}18$ per cent. The model ages of the stars calculated in this study are compatible with those reported in the literature for NGC 6811.
An Independent Evolutionary Origin for Insect Deterrent Cucurbitacins inIberis amara
Authors: Dong Lemeng , Almeida Aldo , Pollier Jacob , Khakimov Bekzod , Bassard Jean-Etienne , Miettinen Karel , Stærk Dan , Mehran Rahimi , Olsen Carl Erik , Motawia Mohammed Saddik , Goossens Alain , Bak Søren
Published: July 2021

Pieris rapae and Phyllotreta nemorum are Brassicaceae specialists, but do not feed on Iberis amara spp. that contain cucurbitacins. The cucurbitacins are highly oxygenated triterpenoid, occurring widespread in cucurbitaceous species and in a few other plant families. Using de novo assembled transcriptomics from I. amara, gene co-expression analysis and comparative genomics, we unraveled the evolutionary origin of the insect deterrent cucurbitacins in I. amara. Phylogenetic analysis of five oxidosqualene cyclases and heterologous expression allowed us to identify the first committed enzyme in cucurbitacin biosynthesis in I. amara, cucurbitadienol synthase (IaCPQ). In addition, two species-specific cytochrome P450s (CYP708A16 and CYP708A15) were identified that catalyze the unique C16 and C22 hydroxylation of the cucurbitadienol backbone, enzymatic steps that have not been reported before. Furthermore, the draft genome assembly of I. amara showed that the IaCPQ was localized to the same scaffold together with CYP708A15 but spanning over 100 kb, this contrasts with the highly organized cucurbitacin gene cluster in the cucurbits. These results reveal that cucurbitacin biosynthesis has evolved convergently via different biosynthetic routes in different families rather than through divergence from an ancestral pathway. This study thus provides new insight into the mechanism of recurrent evolution and diversification of a plant defensive chemical.