bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of intravenous and buccal caffeine for reversal of adverse effects of regadenason
Authors: Stringer BF , Elsadany M , Bote J , Duvall WL
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background/Introduction

Regadenason is a common coronary vasodilator for myocardial perfusion imaging (MPI). Use has been associated with side effects including dyspnea, gastrointestinal upset and chest discomfort. Aminophylline is a common reversal agent. Due to frequent shortages caffeine has emerged as an alternative treatment.

Purpose

Our study aimed to compare the efficacy of intravenous (IV) caffeine and buccal caffeine strips for reversal of regadenason adverse effects.

Methods

Consecutive patients undergoing regadenoson stress SPECT MPI were assessed for the occurrence of symptoms during testing over an 11 week period at a single metropolitan hospital. Adverse symptoms, including their severity and duration, were recorded at the time of testing. Patient satisfaction was rated on a scale of 1 to 5 (5 being the most satisfied). Patients received reversal with caffeine if symptoms were felt to be significant enough by the patient and physician performing the test. The treatment received alternated week to week between IV caffeine (60mg) or 100 mg buccal caffeine strips. Caffeine was given at least 3 minutes after tracer injection. A rescue dose of IV caffeine was offered 10 minutes later if indicated.

Results

Of the 122 patients enrolled in the study, 70 (57%) were included during buccal caffeine weeks and 52 (43%) during IV caffeine weeks, and only 28 (23.9%) received reversal with a caffeine agent. Seven (5.7%) received IV caffeine and 21 (17.2%) received buccal caffeine. The most common adverse symptom reported was dyspnea, which occurred in 54 patients (44.3%). There was no significant difference in symptom duration between IV and buccal caffeine after treatment (152.8 vs 163.4 sec, p = 0.87). There was no significant difference in initial and final symptom severity between groups. Only 2 patients in the buccal group required rescue IV caffeine for ongoing symptoms and emesis. None of the IV group required rescue dose. There was no significant difference in patient satisfaction between the groups (2.8 vs 3.2, p = 0.38). Interestingly, patients were more likely to receive treatment on buccal caffeine weeks compared to IV weeks (30.0% vs 13.5%, p = 0.049)

Conclusion(s)

Buccal caffeine is an effective alternative to IV caffeine for the management of adverse effects from regadenason and may be a more cost effective option. Buccal caffeine is easier to store and prepare than IV caffeine, and compared to other oral caffeine alternatives provides consistent dosing and easier consumption.
Relationship between coronary artery calcium score and myocardial blood flow reserve in patients with suspected coronary artery disease
Authors: Qarajeh R , Peri-Okonny P , Sperry BW , Chan PS , Spertus JA , Thompson RC , Bateman TM , Patel FS , Mcghie AI , Patel KK
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Both the Coronary Artery Calcium Score (CACS), a non-invasive surrogate for atherosclerotic burden, and reduced myocardial blood flow reserve (MBFR) with normal perfusion, a non-invasive surrogate for coronary vasomotor dysfunction, independently predict future cardiovascular events. The relationship between CACS and MBFR, and potential clinical factors affecting it, is not well understood.

Methods

Among 9467 consecutive patients without known history of CAD who had normal perfusion on 82Rb PET-CT and a concomitantly measured CACS between 01/2010 - 06/2020 within our health system, we assessed the relationship between CACS and MBFR. Multiple linear regression was used to predict MBFR using CACS, adjusted for age, sex, BMI, risk factors, symptoms, resting LVEF and vital signs. Interactions of age, sex, diabetes, and symptoms with CACS were assessed to evaluate if they modified the relationship of CACS with MBFR.

Results

Mean age (SD) of the study cohort was 66.4 (12.6) years, 64% were women, 64% had chest pain and 47% had dyspnea. Reduced MBFR (<2) was present in 44% and CAC >0 in 74% of patients.  There was a modest inverse correlation between MBFR and CACS, r= - 0.18, p = < 0.0001 (Figure). In adjusted analyses, CACS (β for CAC per 100 = -0.013 [95% CI: -0.015, -0.010]) was weakly associated with MBFR, and age, sex, diabetes, or symptoms did not modify this relationship (all interaction p-values >0.1). Older age, female sex, presence of hypertension, diabetes, dyspnea, lower LVEF, higher baseline HR and higher CACS independently predicted reduced MBFR, but explained only 20% of the variance in MBFR (R2 =0.20).

Conclusion

There is a weak relationship between CACS and MBFR, which is not modified by age, sex, symptoms, or other CV risk factors. Coronary calcium burden does not completely reflect the overall disease activity within the coronary circulation, and measures of coronary vasomotor function such as MBFR may offer complementary information on CAD risk to that provided by the total burden of calcified atherosclerosis.
Cardiac microcalcification burden is associated with cardiac fat variables in high cardiovascular risk patients
Authors: Borges-Rosa J , Oliveira-Santos M , Silva R , Pereira Da Silva N , Abrunhosa A , Castelo-Branco M , Goncalves L , Ferreira MJ
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Calcification plays a major role in coronary atherogenesis. Positron emission tomography (PET) imaging with fluorine-18 sodium fluoride (Na[18F]F) is able to detect microcalcification and is associated with cardiovascular (CV) risk factors. Thoracic fat volume (TFV) and epicardial adipose tissue (EAT) are associated with atherosclerosis, pro-inflammatory state, and CV events.

Purpose

We aimed to evaluate the association between Na[18F]F uptake and cardiac fat variables.

Methods

Cardiac Na[18F]F uptake was assessed as global molecular calcification score (GMCS): the sum of the product of the mean standardized uptake value times the area of the cardiac regions of interest times the slice thickness for all cardiac transaxial slices, divided by the total number of slices. TFV was assessed in computed tomography (CT) using automated software to sum the voxels consisting of fat (threshold of -190 to -30 Hounsfield units) between the bifurcation of pulmonary artery and the end of pericardial sac. EAT was segmented manually tracing the counter of the pericardium with 3DSlicer and the final volume calculated using the dedicated software. Coronary artery calcium score (CAC) was measured with dedicated software for calcium scoring (GE Healthcare Advantage Workstation 4.2).

Results

Thirty-four high CV risk individuals without previous CV events (50% with ≥5 CV risk factors) were retrospectively scanned with Na[18F]F PET-CT. Mean age is 63.5 ± 7.8 years and 62% male. Median values are: GMCS 320.9 (240.8-402.8), TFV 167.8 (131.4-211.3) mL, EAT 81.3 (60.7-107.2) cm3, and CAC 0.0 (2.5-20.0). There is a positive correlation between GMCS and abdominal perimeter (rs = 0.74), weight (rs = 0.61), TFV (rs = 0.47), and EAT (rs = 0.41), all with p ≤ 0.01. Thoracic and epicardial fat volumes are strongly correlated (rs = 0.80, p < 0.01). Both TFV and EAT are correlated with abdominal perimeter (rs = 0.60, p < 0.01 and rs = 0.46, p < 0.01, respectively) and weight (rs = 0.47, p < 0.01 and rs = 0.42, p = 0.01, respectively). GMCS [356.7 (321.0-409.6) vs. 261.1 (225.6-342.1), p = 0.01] and thoracic fat volume [184.3 (153.2-303.7) vs. 142.1 (90.0-173.1) mL, p = 0.01] are higher in patients with ≥5 CV risk factors, but not EAT [92.5 (62.0-145.7) vs. 76.7 (56.2-86.8) cm3, p = 0.14]. Neither GMCS (rs=-0.06, p = 0.77), TFV (rs = 0.20, p < 0.32) nor EAT (rs = 0.06, p < 0.76) are correlated with CAC score.

Conclusions

In this exploratory analysis with high CV risk patients, the global cardiac microcalcification burden assessed by GMCS is associated with TFV and EAT, but there was no correlation between these variables and CAC. We hypothesize that both GMCS and cardiac fat variables might help to identify higher-risk patients in earlier phases than traditional CT.
Survival Outcome with Routine Clinical Use of 82Rb PET/CT Myocardial Blood Flow (MBF) Quantification
Authors: Wan S , Speechly-Dick ME , Menezes LJ , Endozo R , Bell R , Walker M , Ganeshan B , Dickson J , Kayani I , Groves AM
Published: July 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): NIHR Biomedical Research Centre, University College London Hospitals

Background

The prognostic value of 82Rb PET/CT derived myocardial blood flow (MBF) is increasingly recognised in both general and specific cardiovascular populations.

Purpose

This study investigates the prognostic potential of MBF in a large cohort of patients undergoing routine 82Rb PET/CT examination.

Methods

1148 consecutive patients (687 males, mean age 64 +/- 12 years) whom had been referred for 82Rb PET/CT examination in a single centre were included in this study.  All patients completed a stress 82Rb PET/CT with adenosine infusion, paired with a rest study.  Dynamic PET acquisitions were performed in both. Cardiovascular risk factors were documented as per clinical routine. Images were checked for quality and analysed using a proprietary software by an experienced operator to derive MBF parameters.  Overall survival was recorded following the study.

Results

Median follow-up period was 71 +/- 28 months.  Mean survival was 121 (95% CI: 118-124) months. On univariate analysis, global myocardial flow reserve <1.77 was associated with a higher all-cause mortality (p < 0.001). Other parameters including higher age (> =76 years), lower BMI (<21), qualitative abnormality on the myocardial perfusion scan (MPS), low hyperaemic ejection fraction on the gated studies (stress < 37 and rest < 34). Patients being on cardiac glycosides and diuretics were also significant predictor of poor prognosis (p < 0.001) on univariate analysis, presumably reflecting underlying arrhythmia and heart failure. A multivariate Cox regression analysis (step-wise Forward Wald), comprising of the above significant univariate markers, highlighted global myocardial flow reserve (HR: 2.6, 95%CI: 1.8-3.6, p < 0.001), age (HR: 2.8, 95%CI: 2.0-3.9, p < 0.001),, BMI (HR: 2.7, 95%CI: 1.7-4.1, p < 0.001),, ejection fraction (stress - HR: 3.3, 95%CI: 2.3-4.8, p < 0.001), MPS (HR: 1.5, 95%CI: 1.1-2.1, p = 0.024), and patients on diuretics (HR: 1.8, 95%CI: 1.2-2.5, p = 0.003) were independent predictors of overall survival (overall model: p < 0.001)

Discussion

We show that high volume routinely derived MBF in patients undergoing 82Rb PET/CT is a strong predictor of mortality and independent of other risk factors. This has important clinical implication for measuring not only interventional treatment but also measuring the effect of lifestyle and medical strategies.
Comprehensive mechanical & metabolic imaging of abdominal aortic aneurysm with 4D flow/ FDG PET on an integrated PETMRI: a feasibility study
Authors: Wan S , Steeden J , Rega M , Hoy L , Walls D , Endozo R , Hoath J , Shortman R , Agu O , Menezes L , Muthurangu V , Groves AM
Published: July 2021

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): NIHR Biomedical Research Centre, University College London Hospitals.

Background

A number of non-invasive imaging derived parameters have been implicated in the development and progression of abdominal aortic aneurysm, although the mechanism, and relationships of many of these are yet to be precisely determined.  Mechanical parameters can now be studied using 4D phase contrast magnetic resonance (PCMR), and inflammatory cellular activity can be detected with FDG PET.

Purpose

It may be postulated that inflammation of the aortic wall may be the intermediary at the tissue level linking mechanical wall shear stress (WSS) to aneurysm progression. It may be feasible to study 4D PCMR and FDG PET at the same patient visit on a PETMRI platform, with the potential to enhance temporal and spatial co-registration and improving the understanding of any relationship between these two parameters.  Our study aims to assess feasibility of studying these on an integrated PETMRI system.

Methods

7 patients with known aortic aneurysm were recruited in a vascular ultrasound screening follow up clinic.  During a single visit following 6 hours fasting, all patients underwent FDG injection and 60 minutes uptake period.  With quiet breathing, list mode PET acquisition and concurrent 4D PCMR was acquired using stacks of spiral acquisition, with ECG trace information for retrospective gating.  Images from the 4D PCMR and FDG PET were assessed qualitatively for image quality and visual matching.

Results

All 7 patients completed the study.  Overall image quality was adequate to good.  There is qualitatively a good concordance with impression of positive correlation between wall shear stress and inflammatory signal (see attached image).

Conclusion

We have demonstrated feasibility of combined assessment of mechanical and metabolic imaging parameters using an integrated PETMRI system.  Initial findings show there to be a broad concordance of wall shear stress and inflammatory signal in the abdominal aneurysm.
The prognostic role of PET myocardial perfusion imaging in patients with cardiac sarcoidosis: a systematic review
Authors: Ahmed AI , Tsehay A , Han Y , Alnabelsi T , Agrawal T , Kassi M , Aljizeeri A , Taylor A , Tleyjeh I , Al-Mallah MH
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Sarcoidosis is a multi-systemic inflammatory disease of unknown etiology. Cardiac Sarcoidosis (CS) has been reported in as much as 25% of patients with systemic involvement. 18Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) has a high diagnostic sensitivity/specificity in the diagnosis of CS.

Purpose

The aim of this review is to summarize evidence on the prognostic role of FDG PET.

Methods

Studies were identified by searching MEDLINE from inception to October 2020. Medical Subject Headings (MeSH) terms for sarcoidosis; cardiac and FDG PET imaging were used. Studies of any design assessing the prognostic role of FDG PET in patients with either suspected or confirmed cardiac sarcoidosis imaging done at baseline were included. Abnormal PET was defined as abnormal metabolism (presence of focal or focal-on-diffuse uptake of FDG) OR abnormal metabolism and a perfusion defect. Studies reporting any outcome measure were included. Pooled risk ratio for the composite outcome of MACE was done.

Results

A total of 6 studies were selected for final inclusion (515 patients, 53.4% women, 19.8% racial minorities.) Studies were institution based, retrospective in design and enrolled consecutive patients. All were observational in nature and published in English. All studies used a qualitative assessment of PET scans (abnormal FDG uptake with or without abnormal perfusion). Two studies assessed quantitative metrics (summed stress score in segments with abnormal FDG uptake, standardized uptake value and cardiac metabolic activity.) All studies reported Major Adverse Cardiovascular Events (MACE) as a composite outcome. After a mean follow up ranging from 1.4 to 4.1 years, there were a total of 105 MACE. All studies included death (either all-cause death or sudden cardiac death) and ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation) as a component of MACE. Four of the six studies adjusted for several characteristics in their analysis. All four studies used Left Ventricular Ejection Fraction (LVEF). However, other adjustment variables were not consistent across studies. Five studies found a positive prognostic association with the primary outcome, two of which assessing right ventricular uptake.

Conclusion

Although available evidence indicates FDG PET can be used in the risk stratification of patients with CS, our findings show further studies are needed to quantify the effect in this patient group.
Should oral anticoagulants still be prescribed to patients with atrial fibrillation with a single stroke risk factor but at high bleeding risk? A nationwide cohort study
Authors: Chao Tze-Fan , Chan Yi-Hsin , Tuan Ta-Chuan , Liao Jo-Nan , Chen Tzeng-Ji , Lip Gregory Y H , Chen Shih-Ann
Published: July 2021

Aims

To investigate the co-distributions of stroke and bleeding risks in Asian patients with atrial fibrillation (AF) and the clinical benefits of oral anticoagulants (OACs) among AF patients with a single stroke risk factor but at high bleeding risk.

Methods and results

From 1 January 2001 to 31 December 2016, a total of 404 949 AF patients were retrospectively identified from Taiwan National Health Insurance Research Database. Stroke risk was assessed using the CHA2DS2-VASc score and was categorized into low risk (score = 0 for males and 1 for females), intermediate risk (i.e. a single non-sex stroke risk factor; score = 1 for males and 2 for females), and high risk (score ≥2 for males and ≥3 for females). A high risk of bleeding was defined as a HAS-BLED score ≥3. Around 57.5% of AF patients were at high risk for both stroke and bleeding, and most patients (97.6%) with a low stroke risk were also at low risk for bleeding. Around 18.3% of patients with a CHA2DS2-VASc score of 1 (males) or 2 (females) were at high bleeding risk, and the use of OACs in such patients was associated with a lower risk of composite adverse events of ischaemic stroke, intracranial haemorrhage, or mortality (4.19/100 person-years vs. 5.22/100 person-years, adjusted hazard ratio = 0.781, P = 0.04).

Conclusion

For AF patients with an intermediate risk of stroke (i.e. a single non-sex stroke risk factor) but at high bleeding risk, the use of OACs was still significantly associated with a better overall clinical outcome.
A Bookshop of Their Own: Reading and Print in Chartism, 1838–1850
Authors: Hall Robert G
Published: July 2021

To become a Chartist was to enter the world that print had made; to do so, most working men and women relied on a national network of sympathetic publishers, printers and booksellers. At the centre of this Chartist print culture was the bookshop. For some time now, historians have recognised the important contributions of booksellers as Chartist leaders and organisers; however, the role of bookshops in shaping Chartist reading practices and experiences has not really been explored. There has also been a tendency in studies of Chartism and print to focus primarily on the selling and reading of the Northern Star and to underestimate the importance of almanacs, pamphlets and ephemera (such as posters and advertisements). In this article I take as my subject Chartist print in its multiplicity of forms and argue that Chartist bookshops affected the production, circulation and the reading of texts in several different ways. As retailers and publishers, Chartist booksellers provided the working classes with a diverse mix of cheap publications, Chartist and non-Chartist alike, in many different forms; the bookshop itself came to serve as a free and democratic reading site for these publications. Of an inclusive nature, Chartist bookshops were places where oral and print cultures met and where readers read and discussed all kinds of different texts and ideas. In these and other ways, Chartist booksellers challenged many of the practices and conventions of the respectable book trades and at times crossed over into illegal and seditious activities.
Commissural repositioning in bicuspid aortic valve repair: an in vitro acute model to explore and explain different results
Authors: Romagnoni Claudia , Contino Monica , Jaworek Michal , Rosa Rubina , Salurso Eleonora , Perico Francesca , Gelpi Guido , Vismara Riccardo , Fiore Gianfranco Beniamino , Mangini Andrea , Antona Carlo
Published: July 2021

OBJECTIVES

Commissural orientation <160° is a recognized risk factor for bicuspid aortic valve repair failure. Based on this observation, repairing this subtype of aortic valve by reorienting the 2 commissures at 180° has recently been proposed.

METHODS

Nine porcine hearts with aortic annulus diameters of 25 mm were selected. A pathological model of a Sievers 1 bicuspid aortic valve was obtained by suturing the coaptation line between the left and right leaflets. Each heart underwent reimplantation procedures both in the native (120°) and the reoriented (180°) configuration. After the operation, each sample was tested on a pulse duplicator at rest (heart rate 60 beats per min) and with mild exercise (heart rate 90 beats per min) conditions.

RESULTS

No statistically significant difference was noted in mean and peak transvalvular aortic gradients between the 2 configurations at rest (18.6 ± 5 vs 17.5 ± 4 for the mean aortic gradient; 42.8 ± 12.7 vs 36.3 ± 5.8 for the peak aortic gradient) but the group with the 120°-oriented commissures had significantly higher mean transaortic gradients compared to the group with the 180°-oriented commissures at initial exercise stress conditions (30.1 ± 9.1 vs 24.9 ± 3.8; p value 0.002).

CONCLUSIONS

The 180° commissural reorientation of the asymmetrical bicuspid aortic valve does not improve the transvalvular aortic gradient in an acute model at rest conditions, but it could do so under stress situations. Even if it is surgically more complex and time-consuming, this approach could be a good strategy to improve long-term results, particularly in young patients.
In-frame deletion of SPECC1L microtubule association domain results in gain-of-function phenotypes affecting embryonic tissue movement and fusion events
Authors: Goering Jeremy P , Wenger Luke W , Stetsiv Marta , Moedritzer Michael , Hall Everett G , Isai Dona Greta , Jack Brittany M , Umar Zaid , Rickabaugh Madison K , Czirok Andras , Saadi Irfan
Published: July 2021

Patients with autosomal dominant SPECC1L variants show syndromic malformations, including hypertelorism, cleft palate and omphalocele. These SPECC1L variants largely cluster in the second coiled-coil domain (CCD2), which facilitates association with microtubules. To study SPECC1L function in mice, we first generated a null allele (Specc1lΔEx4) lacking the entire SPECC1L protein. Homozygous mutants for these truncations died perinatally without cleft palate or omphalocele. Given the clustering of human variants in CCD2, we hypothesized that targeted perturbation of CCD2 may be required. Indeed, homozygotes for in-frame deletions involving CCD2 (Specc1lΔCCD2) resulted in exencephaly, cleft palate and ventral body wall closure defects (omphalocele). Interestingly, exencephaly and cleft palate were never observed in the same embryo. Further examination revealed a narrower oral cavity in exencephalic embryos, which allowed palatal shelves to elevate and fuse despite their defect. In the cell, wild-type SPECC1L was evenly distributed throughout the cytoplasm and colocalized with both microtubules and filamentous actin. In contrast, mutant SPECC1L-ΔCCD2 protein showed abnormal perinuclear accumulation with diminished overlap with microtubules, indicating that SPECC1L used microtubule association for trafficking in the cell. The perinuclear accumulation in the mutant also resulted in abnormally increased actin and non-muscle myosin II bundles dislocated to the cell periphery. Disrupted actomyosin cytoskeletal organization in SPECC1L CCD2 mutants would affect cell alignment and coordinated movement during neural tube, palate and ventral body wall closure. Thus, we show that perturbation of CCD2 in the context of full SPECC1L protein affects tissue fusion dynamics, indicating that human SPECC1L CCD2 variants are gain-of-function.
Roles and outcomes of thoracoscopic anatomic lung subsegmentectomy for lung cancer
Authors: Kato Hirohisa , Oizumi Hiroyuki , Suzuki Jun , Suzuki Katsuyuki , Takamori Satoshi
Published: July 2021

OBJECTIVES

We performed sublobar resections, including thoracoscopic segmentectomy and subsegmentectomy for small lung cancers, and analysed the results of indications and outcomes of thoracoscopic subsegmentectomy.

METHODS

Between March 2005 and May 2020, 357 consecutive patients underwent thoracoscopic anatomic sublobar resections for lung cancer, including 68 patients undergoing subsegmentectomy. These patients were compared with 289 patients who underwent segmentectomy during the same period.

RESULTS

Subsegmentectomies included mono-/bi-/tri-subsegmentectomies for 34/23/11 of 68 patients, respectively. The median tumour size was 13.5 mm, significantly smaller than tumours in patients who underwent a segmentectomy (P < 0.001). Tumours obtained by mono-subsegmentectomy (11.0 mm) were significantly smaller than bi-/tri-subsegmentectomy (P = 0.028). The proportion of ground-glass opacity-dominant tumours obtained by subsegmentectomy (85.3%) was higher than that obtained by segmentectomy. The proportion of intentional cases satisfying the criteria for sublobar resection was higher than that of segmentectomy cases. Although tumour locations in 40 patients were not identified during surgery, tumours were correctly resected in 39 patients without tumour markers. The median operative time and blood loss were 167 min and 13 ml, significantly shorter and less, respectively, in subsegmentectomy than in segmentectomy patients (P = 0.005, P = 0.006). Duration of drainage and hospitalization were 1 and 5 days, respectively, for subsegmentectomy patients; complications occurred in 6 (8.8%). Outcomes were similar to those of the segmentectomy patients. Although 4 subsegmentectomy patients died of other diseases, none showed cancer recurrence during a mean follow-up of 50 months.

CONCLUSIONS

Thoracoscopic subsegmentectomy can be used for patients with ground-glass opacity-dominant lung cancers <1.5 cm if adequate margins can be secured.
Late surgical conversion of failed Multilayer Flow Modulator stenting in thoraco-abdominal aneurysms
Authors: Salvati Simone , Bilman Victor , Melloni Andrea , Baccellieri Domenico , Kahlberg Andrea , Melissano Germano , Chiesa Roberto , Bertoglio Luca
Published: July 2021

OBJECTIVES

The aim of this study was to report the outcomes of open or hybrid repair of failed thoraco-abdominal aortic aneurysm endovascular treatment with Multilayer Flow Modulator (MFM) stents.

METHODS

All patients who underwent open or hybrid repair of a failed MFM aortic treatment were retrospectively analysed. Perioperative and postoperative data, as well as midterm survival, were assessed.

RESULTS

Between 2013 and 2020, 39 patients received an open or hybrid conversion after endovascular treatment. Five of them [13%; 4 males; median age 68 years (interquartile range 66–76)] were previously treated with aortic MFM stents (Cardiatis, Isnes, Belgium). Among these, the median interval between index repair and conversion was 84 months (interquartile range 75–84). The median aneurysm diameter was 9.6 cm (interquartile range 8–10). Renovisceral vessels steno-occlusion was highly prevalent: 2 renal arteries were occluded; 3 coeliac trunks, 2 renal arteries and 1 superior mesenteric artery had a >70% ostial stenosis. Open standard thoraco-abdominal aneurysm conversion was performed in 3 fit patients, while a hybrid approach with visceral debranching and tube endografting was performed in 2 high-risk patients. Two patients (2 open repairs) died intraoperatively, and 1 (hybrid repair) postoperatively. The 2 successfully treated patients are alive at 4- and 34-month follow-up, respectively, with patent visceral branches.

CONCLUSIONS

Open or hybrid thoraco-abdominal aortic aneurysm treatment after failed endovascular aortic repair with MFM stents might be the only surgical option to address sac enlargements and ruptures or branch-related failures. However, both procedures had a poor prognosis due to both the impaired preoperative patient’s status and the surgical complexity in the presented series.
Computational drug repositioning of atorvastatin for ulcerative colitis
Authors: Bai Lawrence , Scott Madeleine K D , Steinberg Ethan , Kalesinskas Laurynas , Habtezion Aida , Shah Nigam H , Khatri Purvesh
Published: July 2021

Objective

Ulcerative colitis (UC) is a chronic inflammatory disorder with limited effective therapeutic options for long-term treatment and disease maintenance. We hypothesized that a multi-cohort analysis of independent cohorts representing real-world heterogeneity of UC would identify a robust transcriptomic signature to improve identification of FDA-approved drugs that can be repurposed to treat patients with UC.

Materials and Methods

We performed a multi-cohort analysis of 272 colon biopsy transcriptome samples across 11 publicly available datasets to identify a robust UC disease gene signature. We compared the gene signature to in vitro transcriptomic profiles induced by 781 FDA-approved drugs to identify potential drug targets. We used a retrospective cohort study design modeled after a target trial to evaluate the protective effect of predicted drugs on colectomy risk in patients with UC from the Stanford Research Repository (STARR) database and Optum Clinformatics DataMart.

Results

Atorvastatin treatment had the highest inverse-correlation with the UC gene signature among non-oncolytic FDA-approved therapies. In both STARR (n = 827) and Optum (n = 7821), atorvastatin intake was significantly associated with a decreased risk of colectomy, a marker of treatment-refractory disease, compared to patients prescribed a comparator drug (STARR: HR = 0.47, P = .03; Optum: HR = 0.66, P = .03), irrespective of age and length of atorvastatin treatment.

Discussion & Conclusion

These findings suggest that atorvastatin may serve as a novel therapeutic option for ameliorating disease in patients with UC. Importantly, we provide a systematic framework for integrating publicly available heterogeneous molecular data with clinical data at a large scale to repurpose existing FDA-approved drugs for a wide range of human diseases.
Complex abdominal wall reconstruction after massive resection due to neoplastic invasion: a case report
Authors: Piltcher-da-Silva Rodrigo , Hütten Débora Oliveira , Locks-Coelho Lucas Dorídio , Piltcher-Recuero Mariana , Volkweis Bernardo Silveira , Tarta Cláudio , Appel Márcia Luiza , Cavazzola Leandro Totti
Published: July 2021

Complex reconstructions of the abdominal wall, necessary after resection of neoplasms, infection or trauma, are a challenge for the surgical team. Although ovarian carcinoma is commonly presented with peritoneal carcinomatosis and invasion of adjacent organs, it rarely can invade the abdominal wall. Invasion of the abdominal wall was documented on ultrasound and abdominal computed tomography. Surgery was discussed and performed in a multidisciplinary team and consisted of wide en bloc excision and reconstruction with open intraperitoneal onlay mesh with inorganic polypropylene-coated mesh (Bard/BD Sepramesh), a midweight macroporous mesh and abdominoplasty. Postoperative course was uneventful and the patient showed good evolution 1 year after the procedure. Our report highlights the main objectives in complex reconstructions, the importance of a multidisciplinary team and discusses the characteristics that the mesh must have in order to achieve the desired goal.
Breeding habitat selection of urban peregrine falcons (Falco peregrinus) in London
Authors: Mak Brandon , Francis Robert A , Chadwick Michael A
Published: July 2021

Understanding habitat selection by individual animals within their home range is crucial to facilitating their conservation. Peregrine falcon (Falco peregrinus) populations are increasingly urbanised, but little is known about their urban habitat use. In this study, we analysed the breeding habitat selection of peregrine falcons in London, United Kingdom, based on nest site locations identified through records of public sightings submitted to an online database between 2003 and 2018. We found peregrines displayed a preference for nesting in proximity to waterbodies, built-up areas and public parks and gardens, while wooded, agricultural and allotments areas were least preferred. We hypothesise that peregrines seek contrasting topography that proves advantageous for hunting in the vicinity of their nests, resulting in their selection of breeding sites within tall buildings that are adjacent to suitable foraging areas. From these findings, we conclude that (i) social drivers such as demand for green spaces and waterbodies near buildings shape peregrine nesting opportunities in the city and (ii) for urban planning to support conservation, we need further understanding of how each type of greenspace may be used differentially by raptors.
Habitat use by wandering pet cats (Felis catus) in a patchy urban environment
Authors: Fardell Loren L , Young Lauren I , Pavey Chris R , Dickman Christopher R
Published: July 2021

Pet cats (Felis catus) often have negative effects on wildlife. This is of growing concern in urban areas as these are increasingly becoming hotspots of native wildlife activity, and as the human population increases, so too does the pet cat population. To maintain biodiversity in urban areas, further knowledge on pet cat behaviour and impacts is required so that management strategies for pet cats are well informed and have public and government support. Here, we offer insights into the wandering activity of pet cats in a patchy urban—heavily vegetated landscape on the east coast of Australia. Our estimated pet cat movement ranges were generally larger than those previously observed in similar landscapes, as well as in more urbanized and rural habitats. Using GPS data loggers, we found that pet cats did not utilize vegetated spaces more than urban areas, nor did they prefer them relative to their availability. Half of our study cats selected urban habitats, whilst the other half displayed no selection or a slight preference for vegetated spaces; these cats had fewer barriers to overcome to reach them. We did not observe any large differences in movements or habitat use between day and night, but displacement distances and preference for vegetated space habitat were marginally lower at night. All pet cats monitored spent most of their time outside their houses. As both urban and vegetated spaces in patchy urban landscapes provide habitat for native wildlife, pet cat activity across both habitat types requires management action.
Derepression of specific miRNA-target genes in rice using CRISPR/Cas9
Authors: Lin Yarong , Zhu Yiwang , Cui Yuchao , Chen Rui , Chen Zaijie , Li Gang , Fan Meiying , Chen Jianmin , Li Yan , Guo Xinrui , Zheng Xijun , Chen Liang , Wang Feng
Published: July 2021

MicroRNAs (miRNAs) target specific mRNA molecules based on sequence complementarity for their degradation or repression of translation, thereby regulating various developmental and physiological processes in eukaryotic organisms. Expressing the target mimicry (MIM) and short tandem target mimicry (STTM) can block endogenous activity of mature miRNAs and eliminate the inhibition of their target genes, resulting in phenotypic changes due to higher expression of the target genes. Here, we report a strategy to achieve derepression of interested miRNA-target genes through CRISPR/Cas9-based generation of in-frame mutants within the miRNA-complementary sequence of the target gene. We show that two rice genes, OsGRF4 (GROWTH REGULATING FACTOR 4) and OsGRF8 carrying in-frame mutants with disruption of the miR396 recognition sites, escape from miR396-mediated post-transcriptional silencing, resulting in enlarged grain size and increase in brown planthopper (BPH) resistance, in their respective transgenic rice lines. These results demonstrate that CRISPR/Cas9-mediated disruption of miRNA target sites can be effectively employed to precisely derepress particular target genes of functional importance for trait improvement in plants.
Combinations of Ghd7, Ghd8, and Hd1 determine strong heterosis of commercial rice hybrids in diverse ecological regions
Authors: Zhou Xiangchun , Nong Chunxiao , Wu Bi , Zhou Tianhao , Zhang Bo , Liu Xingshao , Gao Guanjun , Mi Jiaming , Zhang Qinglu , Liu Haiyang , Liu Shisheng , Li Zhixin , He Yuqing , Mou Tongmin , Guo Sibin , Li Shaoqing , Yang Yuanzhu , Zhang Qifa , Xing Yongzhong
Published: July 2021

Heterosis of grain yield is closely associated with heading date in crops. Gene combinations of the major heading date genes Ghd7, Ghd8, and Hd1 play important roles in enhancing grain yield and adaptation to ecological regions in rice. However, the predominant three-gene combinations for a specific ecological region remain unclear in both three-line and two-line hybrids. In this study, we sequenced these three genes of 50 cytoplasmic male sterile/maintainer lines, 31 photo-thermo-sensitive genic male sterile lines, and 109 restorer lines. Sequence analysis showed that hybrids carrying strong functional alleles of Ghd7 and Hd1 and non-functional Ghd8 are predominant in three-line hybrids and are recommended for rice production in the subtropics around 30°N/S. Hybrids carrying strong functional Ghd7 and Ghd8 and non-functional Hd1 are predominant in two-line hybrids and are recommended for low latitude areas around 23.5°N/S rich in photothermal resources. Hybrids carrying strong functional Ghd7 and Ghd8 and functional Hd1 were not identified in commercial hybrids in the middle and lower reaches of the Yangtze River, but they have high yield potential in tropical regions because they have the strongest photoperiod sensitivity. Based on these findings, two genic sterile lines, Xiangling 628S and C815S, whose hybrids often head very late, were diagnosed with these three genes, and Hd1 was targeted to be knocked out in Xiangling 628S and replaced with hd1 in C815S. The hybrids developed from both modified sterile lines in turn had appropriate heading dates and significantly improved grain yield. This study provides new insights for breeding design to develop hybrids for various regions.
Protein kinase and phosphatase control of plant temperature responses
Authors: Praat Myrthe , De Smet Ive , van Zanten Martijn
Published: July 2021

Plants must cope with ever-changing temperature conditions in their environment. Suboptimal high and low temperatures and stressful extreme temperatures induce adaptive mechanisms that allow optimal performance and survival, respectively. These processes have been extensively studied at the physiological, transcriptional, and (epi)genetic level. Cellular temperature signalling cascades and tolerance mechanisms also involve post-translational modifications (PTMs), particularly protein phosphorylation. Many protein kinases are known to be involved in cold acclimation and heat stress responsiveness, but the role and importance of kinases and phosphatases in triggering responses to mild changes in temperature, such as thermomorphogenesis, are inadequately understood. In this review, we summarize current knowledge on the roles of kinases and phosphatases in plant temperature responses. We discuss how kinases can function over a range of temperatures in different signalling pathways and provide an outlook to the application of PTM-modifying factors for the development of thermotolerant crops.
Host galaxies of high-redshift quasars: SMBH growth and feedback
Authors: Valentini Milena , Gallerani Simona , Ferrara Andrea
Published: July 2021

The properties of quasar-host galaxies might be determined by the growth and feedback of their supermassive black holes (SMBHs, 108−10 M⊙). We investigate such connection with a suite of cosmological simulations of massive (halo mass ≈1012 M⊙) galaxies at z ≃ 6 that include a detailed subgrid multiphase gas and accretion model. BH seeds of initial mass 105 M⊙ grow mostly by gas accretion, and become SMBH by z = 6 setting on the observed MBH−M⋆ relation without the need for a boost factor. Although quasar feedback crucially controls the SMBH growth, its impact on the properties of the host galaxy at z = 6 is negligible. In our model, quasar activity can both quench (via gas heating) or enhance (by interstellar medium overpressurization) star formation. However, we find that the star formation history is insensitive to such modulation as it is largely dominated, at least at z > 6, by cold gas accretion from the environment that cannot be hindered by the quasar energy deposition. Although quasar-driven outflows can achieve velocities $\gt 1000~\rm km~s^{-1}$, only ≈4 per cent of the outflowing gas mass can actually escape from the host galaxy. These findings are only loosely constrained by available data, but can guide observational campaigns searching for signatures of quasar feedback in early galaxies.
Radiation hydrodynamics simulations of massive star cluster formation in giant molecular clouds
Authors: Fukushima Hajime , Yajima Hidenobu
Published: July 2021

By performing 3D radiation hydrodynamics simulations, we study the formation of young massive star clusters (YMCs; M* > 104 M⊙) in clouds with the surface density ranging from Σcl = 80 to 3200 M⊙ pc−2. We find that photoionization feedback suppresses star formation significantly in clouds with low-surface density. Once the initial surface density exceeds ∼100 M⊙ pc−2 for clouds with Mcl = 106 M⊙ and Z = Z⊙, most of the gas is converted into stars because the photoionization feedback is inefficient in deep gravitational potential. In this case, the star clusters are massive and gravitationally bounded as YMCs. The transition surface density increases as metallicity decreases, and it is ∼350 M⊙ pc−2 for Z = 10−2 Z⊙. We show that more than 10 per cent of star formation efficiency (SFE) is needed to keep a star cluster gravitationally bounded even after the disruption of a cloud. Also, we develop a semi-analytical model reproducing the SFEs obtained in our simulations. We find that the SFEs are fit with a power-law function with the dependence ${\propto}\Sigma _{\rm cl}^{1/2}$ for low-surface density and rapidly increases at the transition surface densities. The conditions of the surface density and the metallicity match recent observations of giant molecular clouds forming YMCs in nearby galaxies.
Endogenous piRNA-guided slicing triggers responder and trailer piRNA production from viral RNA inAedes aegyptimosquitoes
Authors: Joosten Joep , Overheul Gijs J , Van Rij Ronald P , Miesen Pascal
Published: July 2021

In the germline of animals, PIWI interacting (pi)RNAs protect the genome against the detrimental effects of transposon mobilization. In Drosophila, piRNA-mediated cleavage of transposon RNA triggers the production of responder piRNAs via ping-pong amplification. Responder piRNA 3′ end formation by the nuclease Zucchini is coupled to the production of downstream trailer piRNAs, expanding the repertoire of transposon piRNA sequences. In Aedes aegypti mosquitoes, piRNAs are generated from viral RNA, yet, it is unknown how viral piRNA 3′ ends are formed and whether viral RNA cleavage gives rise to trailer piRNA production. Here we report that in Ae. aegypti, virus- and transposon-derived piRNAs have sharp 3′ ends, and are biased for downstream uridine residues, features reminiscent of Zucchini cleavage of precursor piRNAs in Drosophila. We designed a reporter system to study viral piRNA 3′ end formation and found that targeting viral RNA by abundant endogenous piRNAs triggers the production of responder and trailer piRNAs. Using this reporter, we identified the Ae. aegypti orthologs of Zucchini and Nibbler, two nucleases involved in piRNA 3′ end formation. Our results furthermore suggest that autonomous piRNA production from viral RNA can be triggered and expanded by an initial cleavage event guided by genome-encoded piRNAs.
PetM Is Essential for the Stabilization and Function of the Cytochrome b6f Complex in Arabidopsis
Authors: Lan Yixin , Chen Qi , Kong Mengmeng , Liu Yanyun , Lyu Ming-Ju Amy , Perveen Shahnaz , Mi Hualing
Published: July 2021

The cytochrome b6f (cyt b6f) acts as a common linker of electron transport between photosystems I and II in oxygenic photosynthesis. PetM, one of eight subunits of the cyt b6f complex, is a small hydrophobic subunit at the outside periphery, the functional mechanism of which remains to be elucidated in higher plants. In this work, we found that unlike the PetM mutant in Synechocystis sp. PCC 6803, the Arabidopsis thaliana PetM mutant showed a bleached phenotype with yellowish leaves, block of photosynthetic electron transport and loss of photo-autotrophy, similar to the Arabidopsis PetC mutant. Although PetM is relatively conserved between higher plants and cyanobacteria, Synechocystis PetM could not rescue the PetM-knockout phenotype in Arabidopsis. We provide evidence that the Synechocystis PetM did not stably bind to the Arabidopsis cyt b6f complex. Based on these results, we suggest that PetM is required by Arabidopsis to maintain the function of the cyt b6f complex, likely through its close link with core subunits to form a tight ‘fence’ that stabilizes the core of the complex.
Green’s functions for an anisotropic elastic parabolic inhomogeneity under generalised plane strain deformations
Authors: Wang X , Schiavone P
Published: July 2021

On the basis of the Stroh sextic formalism, we propose a novel method to derive Green’s functions for a two-phase composite composed of an anisotropic elastic parabolic inhomogeneity perfectly bonded to an anisotropic elastic matrix. The composite is subjected to a line force and a line dislocation, which can be located anywhere inside or outside the inhomogeneity or on the parabolic interface itself. Explicit expressions describing the analytic vector function defined in the parabolic inhomogeneity are derived for each of the three aforementioned cases associated with the location of the line force and line dislocation. When the line dislocation is located inside the parabolic inhomogeneity, the image force acting on the line dislocation is expediently derived using the Peach–Koehler formula.
Low vitamin D levels and prognosis in a COVID-19 pediatric population: a systematic review
Authors: Shah K , Varna V P , Pandya A , Saxena D
Published: July 2021

We aim to study the relationship between vitamin D level, risk and severity of Coronavirus disease of 2019 (COVID-19) infection in pediatric population through systematic review. We searched PubMed, CINAHL, EMBASE, Cochrane Library and Google Scholar from December 2019 to June 2021 for retrieving articles studying association between vitamin D deficiencies with COVID-19. Qualitative details were synthesized in evidence table and quantitative data was used for deriving pooled estimate through meta-analysis. After initial search of 2261 articles, eight eligible studies (two reviews) were included in the systematic review. Meta-analysis of the quantitative data (six studies) showed pooled prevalence of vitamin D deficiency as 45.91% (95% CI: 25.148–67.450). In infected pediatric patients, low levels of vitamin D increased the risk of severe disease (odds ratio–5.5; 95% CI: 1.560–19.515; P = 0.008). It was also found that children and adolescents having vitamin D deficiency had greater risk of COVID infection as compared to patients with normal vitamin D levels. Improvement in disease severity with vitamin D supplementation was also noted. The systematic review showed that almost half of the pediatric COVID patients suffer from vitamin D deficiency. It is also clear that the low level of vitamin D is associated with greater risk of infection and poorer outcome in pediatrics.
Probability Density Functions Attached to Random Euler Products for Automorphic L-Functions
Authors: Mine Masahiro
Published: July 2021

In this paper, we study the value distributions of L-functions of holomorphic primitive cusp forms in the level aspect. We associate such automorphic L-functions with probabilistic models called the random Euler products. First, we prove the existence of probability density functions attached to the random Euler products. Then various mean values of automorphic L-functions are expressed as integrals involving the density functions. Moreover, we estimate the discrepancies between the distributions of values of automorphic L-functions and those of the random Euler products.