bluuebunny/crossref_metadata_2025 huggingface dataset:
The synthesis and characterization of a new diphosphine-protected gold hydride nanocluster
Authors: Dong Jia , Gao Ze-Hua , Wang Lai-Sheng
Published: July 2021

Gold is the most inert metal and does not form a bulk hydride. However, gold becomes chemically active in the nanometer scale and gold nanoparticles have been found to exhibit important catalytic properties. Here, we report the synthesis and characterization of a highly stable ligand-protected gold hydride nanocluster, [Au22H3(dppee)7]3+ [dppee = bis(2-diphenylphosphino) ethyl ether]. A synthetic method is developed to obtain high purity samples of the gold trihydride nanocluster with good yields. The properties of the new hydride cluster are characterized with different experimental techniques, as well as theoretical calculations. Solid samples of [Au22H3(dppee)7]3+ are found to be stable under ambient conditions. Both experimental evidence and theoretical evidence suggest that the Au22H3 core of the [Au22H3(dppee)7]3+ hydride nanocluster consists of two Au11 units bonded via two triangular faces, creating six uncoordinated Au sites at the interface. The three H atoms bridge the six uncoordinated Au atoms at the interface. The Au11 unit behaves as an eight-electron trivalent superatom, forming a superatom triple bond (Au11 ≡ Au11) in the [Au22H3(dppee)7]3+ trihydride nanocluster assisted by the three bridging H atoms.
Molecular droplets vs bubbles: Effect of curvature on surface tension and Tolman length
Authors: Wen Jun , Dini Daniele , Hu Haibao , Smith Edward R.
Published: July 2021

Droplets and bubbles are thought to be two sides of the same coin; this work determines how true this is at the molecular scale. Stable cylindrical nanodroplets and nanobubbles are obtained in Molecular Dynamics (MD) simulations with three-phase contact lines pinned by alternate hydrophobic and hydrophilic patterns. The surface tension and Tolman length for both types of curved interfaces are obtained with the Kirkwood–Buff method, based on the difference between normal and tangential pressure components. Both bubble and droplet cases are compared to the flat interface case for reference. Results show that the surface tension decreases linearly while the Tolman length increases linearly with the gas/liquid density ratio. By running a careful parameter study of the flat interface over a range of densities, the effect of the density ratio can be corrected isolating the effects of curvature on the surface tension and Tolman length. It is found that such effects start to be seen when the equimolar curvature radius goes down to 20 reduced Lennard–Jones (LJ) units. They have the same magnitude but act with opposite signs for nanodroplet and nanobubble interfaces. Considering effects of the density ratio and curvature, a fitted Tolman equation was obtained, which predicts the surface tension of a curved interface. Results obtained by the fitted Tolman equation agree well with those obtained by the MD simulations except at very small curvature radius (<10 reduced LJ units) due to the accumulation of the curvature dependence of the Tolman length.
An inverted relativistic magnetron with virtual cathode based on bidirectional electron beams
Authors: Cheng Renjie , Li Tianming , Wang Jiaoyin , Wang Haiyang , Li Hao , Zhou Yihong , Ou Meiling , Hu Biao
Published: July 2021

An improved L-band inverted relativistic magnetron powered by a virtual cathode is presented. An extra emitter is introduced at the end of a slow-wave structure to reduce the desired π mode start-oscillation time, which is critical when short radiation pulses are required. Electrons produced by both upstream and downstream emitters are injected into the interacting space simultaneously, and the rapid increase in electron density in this region accelerates the establishment of a virtual cathode. Furthermore, the additional emitter provides more charged particles for beam–wave interaction, so that the amplitude of output power can be improved. The particle-in-cell simulation demonstrates that a power conversion efficiency of 76.5% could be obtained for a diode voltage of 500 kV and guiding magnetic field of 0.165 T. Compared with the same slow-wave structure powered by a single beam, the output microwave power is increased from 1.1 to 3.1 GW and the startup time is shortened from 53 to 29 ns.
Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation
Authors: Frank Filipp , Liu Xu , Ortlund Eric A.
Published: July 2021

Significance

Antiinflammatory steroid drugs signal through the glucocorticoid receptor (GR) and regulate the expression of specific target genes. It is well known that different GR response elements in regulatory DNA sequences determine if a gene is activated or repressed, but the mechanism for this is unknown. We show that GR forms phase-separated condensates, which specifically enrich transcriptional coregulator proteins. Condensates of GR bound to activating or repressive response elements exhibit different properties and are not miscible with each other. Importantly, binding to activating DNA results in enhanced recruitment of coactivators to GR condensates. This work demonstrates that GR signaling is functionally modulated by phase separation and describes a mechanism for the DNA-dependent up- and down-regulation of GR target genes.
Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies
Authors: Li Shamin , Simoni Yannick , Zhuang Summer , Gabel Austin , Ma Shaokang , Chee Jonathan , Islas Laura , Cessna Anthony , Creaney Jenette , Bradley Robert K. , Redwood Alec , Robinson Bruce W. , Newell Evan W.
Published: July 2021

Significance

Strongly implicated in effective antitumor immune responses, tumor mutation–derived antigens, or neoantigens, are one of the main targets for cancer vaccines despite uncertainty of the efficacy of this approach. Using a high-throughput screening method, we identify an endogenously immunogenic neoantigen in a commonly used mouse lung tumor model. We also found that the endogenous CD8 T cells specific for this neoantigen expand greatly upon treatment with immune checkpoint inhibitors or vaccination despite the lack of associated tumor regression in this model. In addition to informing neoantigen vaccination strategies and providing an accessible system for testing alternative therapeutics, our results provide insights into the mechanisms for the lack of response observed for a majority of patients treated with checkpoint blockade immunotherapies.
The Poet Nefʿī, Fresh Persian Verse, and Ottoman Freshness
Authors: Kim Sooyong
Published: July 2021

Scholars have generally recognized the Ottoman poet Nefʿī (d. 1635) for his refinement of the panegyric in Turkish and his skill in its unflattering twin, the invective. They have thus paid little attention to the fact that he composed poems in Persian, and sufficient to compile a collection of them, simply viewing his output as a byproduct of his taste for the fresh style emanating from the East, particularly India, with no consideration of other factors at play. The article addresses this contextual gap by situating Nefʿī's engagement with the fresh style in relation to wider efforts at poetic renewal and also to literati disputes about the extent to which the fresh style and other currents from the East ought to be adopted and assimilated, in which differing formal and generic preferences, as well as linguistic and rhetorical concerns, were central. The article ultimately suggests that Nefʿī's overall work should be seen as part of those wider efforts that also aimed at making Ottoman practice distinctively fresh.
Evaluating Spin in the Abstracts of Systematic Reviews and Meta-Analyses on Cannabis use Disorder
Authors: Corcoran Adam , Neale Monika , Arthur Wade , Ottwell Ryan , Roberts Will , Hartwell Micah , Cates Stephens , Wright Drew N. , Beaman Jason , Vassar Matt
Published: July 2021

Background: Clinicians rely upon abstracts to provide them quick synopses of research findings that may apply to their practice. Spin can exist within these abstracts that distorts or misrepresents the findings. Our goal was to evaluate the level of spin within systematic reviews (SRs) focused on the treatment of cannabis use disorder (CUD). Methods: A systematic search was conducted in May 2020. To meet inclusion criteria, publications had to be either an SR or meta-analysis related to the treatment of cannabis use. Screening and data extraction was performed in a duplicate and masked fashion. Study quality was assessed using AMSTAR-2 Results: 16/24 SRs (66.7%) contained at least one form of spin in the abstract. The most common forms of spin identified were type 3—s elective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention (45.8%)—and type 8— the review's findings from a surrogate marker or a specific outcome to the global improvement of the disease (37.5%). No significant association between spin and intervention type, PRISMA requirements, or funding source was identified. Weak positive correlations were found between the presence of spin and abstract word count ( r =.217) and between spin and AMSTAR-2 rating ( r = 0.143). “Moderate” was the most common AMSTAR-2 rating (9/24, 37.5%), followed by “low” (7/24, 29.2%) and “critically low” (7/24, 29.2%). One systematic review received an AMSTAR-2 rating of “high” (1/24, 4.2%). Conclusions: Spin was common among abstracts from the SRs focused on the treatments for CUD. Higher quality studies may help reduce the overall rate as well as standardizing treatment outcomes. To facilitate this, we encourage all authors, peer-reviewers, and editors to be more aware of the various types of spin as they can help reduce the overall amount of spin seen within the literature.
PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection
Authors: Oyesola Oyebola O. , Shanahan Michael T. , Kanke Matt , Mooney Bridget M. , Webb Lauren M. , Smita Shuchi , Matheson Macy K. , Campioli Pamela , Pham Duc , Früh Simon P. , McGinty John W. , Churchill Madeline J. , Cahoon Jordan L. , Sundaravaradan Pavithra , Flitter Becca A. , Mouli Karthik , Nadjsombati Marija S. , Kamynina Elena , Peng Seth A. , Cubitt Rebecca L. , Gronert Karsten , Lord James D. , Rauch Isabella , von Moltke Jakob , Sethupathy Praveen , Tait Wojno Elia D.
Published: July 2021

Type 2 inflammation is associated with epithelial cell responses, including goblet cell hyperplasia, that promote worm expulsion during intestinal helminth infection. How these epithelial responses are regulated remains incompletely understood. Here, we show that mice deficient in the prostaglandin D2 (PGD2) receptor CRTH2 and mice with CRTH2 deficiency only in nonhematopoietic cells exhibited enhanced worm clearance and intestinal goblet cell hyperplasia following infection with the helminth Nippostrongylus brasiliensis. Small intestinal stem, goblet, and tuft cells expressed CRTH2. CRTH2-deficient small intestinal organoids showed enhanced budding and terminal differentiation to the goblet cell lineage. During helminth infection or in organoids, PGD2 and CRTH2 down-regulated intestinal epithelial Il13ra1 expression and reversed Type 2 cytokine–mediated suppression of epithelial cell proliferation and promotion of goblet cell accumulation. These data show that the PGD2–CRTH2 pathway negatively regulates the Type 2 cytokine–driven epithelial program, revealing a mechanism that can temper the highly inflammatory effects of the anti-helminth response.
Feasibility of primordial black hole Remnants as dark matter in view of Hawking radiation recoil
Authors: Di Gennaro Sofia , Ong Yen Chin
Published: July 2021

It has recently been suggested that black hole remnants of primordial origin are not a viable dark matter candidate since they would have far too large a velocity due to the recoil of Hawking radiation.
We re-examined this interesting claim in more details and found that it does not rule out such a possibility. On the contrary, for models based on non-commutativity of spacetime near the Planck scale, essentially the same argument can be used to estimate the scale at which the non-commutativity effect becomes important. If dark matter “particles” are non-commutative black holes that have passed the maximum temperature, this implies that the non-commutative scale is about 100 times the Planck length. The same analysis applies to other black hole remnants whose temperature reaches a maximum before cooling off, for example, black holes in asymptotically safe gravity.
Emissions projections for US utilities through 2050
Authors: Grubert Emily
Published: July 2021

Decarbonization is an urgent global policy priority, with increasing movement towards zero-carbon targets in the United States and elsewhere. Given the joint decarbonization strategies of electrifying fossil fuel-based energy uses and decarbonizing the electricity supply, understanding how electricity emissions might change over time is of particular value in evaluating policy sequencing strategies. For example, is the electricity system likely to decarbonize quickly enough to motivate electrification even on relatively carbon-intensive systems? Although electricity sector decarbonization has been widely studied, limited research has focused on evaluating emissions factors at the utility level, which is where the impact of electrification strategies is operationalized. Given the existing fleet of electricity generators, ownership structures, and generator lifespans, committed emissions can be modeled at the utility level. Generator lifespans are modeled using capacity-weighted mean age-on-retirement for similar units over the last two decades, a simple empirical outcome variable reflecting the length of time the unit might reasonably be expected to operate. By also evaluating generators in wholesale power markets and designing scenarios for new-build generation, first-order annual average emissions factors can be projected forward on a multidecadal time scale at the utility level. This letter presents a new model of utility-specific annual average emissions projections (greenhouse gases and air pollutants) through 2050 for the United States, using a 2019 base year to define existing asset characteristics. Enabling the creation and evaluation of scenario-based projections for dynamic environmental intensity metrics in a decarbonizing electricity sector can inform life cycle and other environmental assessment studies that evaluate impact over time, in addition to highlighting particular opportunities and risks associated with the timing and location of long-lived capital investments as the fossil fuel electricity generator fleet turns over. Model results can also be used to contextualize utilities’ decarbonization commitments and timelines against their asset bases.
Genome-wide hierarchical mixed model association analysis
Authors: Hao Zhiyu , Gao Jin , Song Yuxin , Yang Runqing , Liu Di
Published: July 2021

In genome-wide mixed model association analysis, we stratified the genomic mixed model into two hierarchies to estimate genomic breeding values (GBVs) using the genomic best linear unbiased prediction and statistically infer the association of GBVs with each SNP using the generalized least square. The hierarchical mixed model (Hi-LMM) can correct confounders effectively with polygenic effects as residuals for association tests, preventing potential false-negative errors produced with genome-wide rapid association using mixed model and regression or an efficient mixed-model association expedited (EMMAX). Meanwhile, the Hi-LMM performs the same statistical power as the exact mixed model association and the same computing efficiency as EMMAX. When the GBVs have been estimated precisely, the Hi-LMM can detect more quantitative trait nucleotides (QTNs) than existing methods. Especially under the Hi-LMM framework, joint association analysis can be made straightforward to improve the statistical power of detecting QTNs.
A gentle introduction to understanding preclinical data for cancer pharmaco-omic modeling
Authors: Piyawajanusorn Chayanit , Nguyen Linh C , Ghislat Ghita , Ballester Pedro J
Published: July 2021

A central goal of precision oncology is to administer an optimal drug treatment to each cancer patient. A common preclinical approach to tackle this problem has been to characterize the tumors of patients at the molecular and drug response levels, and employ the resulting datasets for predictive in silico modeling (mostly using machine learning). Understanding how and why the different variants of these datasets are generated is an important component of this process. This review focuses on providing such introduction aimed at scientists with little previous exposure to this research area.
A generalizability score for aggregate causal effect
Authors: Chen Rui , Chen Guanhua , Yu Menggang
Published: July 2021

Scientists frequently generalize population level causal quantities such as average treatment effect from a source population to a target population. When the causal effects are heterogeneous, differences in subject characteristics between the source and target populations may make such a generalization difficult and unreliable. Reweighting or regression can be used to adjust for such differences when generalizing. However, these methods typically suffer from large variance if there is limited covariate distribution overlap between the two populations. We propose a generalizability score to address this issue. The score can be used as a yardstick to select target subpopulations for generalization. A simplified version of the score avoids using any outcome information and thus can prevent deliberate biases associated with inadvertent access to such information. Both simulation studies and real data analysis demonstrate convincing results for such selection.
Haematophagous ectoparasites lower survival of and have detrimental physiological effects on golden eagle nestlings
Authors: Dudek Benjamin M , Henderson Michael T , Hudon Stephanie F , Hayden Eric J , Heath Julie A
Published: July 2021

Haematophagous ectoparasites can directly affect the health of young animals by depleting blood volume and reducing energetic resources available for growth and development. Less is known about the effects of ectoparasitism on stress physiology (i.e. glucocorticoid hormones) or animal behaviour. Mexican chicken bugs (Haematosiphon inodorus; Hemiptera: Cimicidae) are blood-sucking ectoparasites that live in nesting material or nest substrate and feed on nestling birds. Over the past 50 years, the range of H. inodorus has expanded, suggesting that new hosts or populations may be vulnerable. We studied the physiological and behavioural effects of H. inodorus on golden eagle (Aquila chrysaetos) nestlings in southwestern Idaho. We estimated the level of H. inodorus infestation at each nest and measured nestling mass, haematocrit, corticosterone concentrations, telomere lengths and recorded early fledging and mortality events. At nests with the highest levels of infestation, nestlings had significantly lower mass and haematocrit. In addition, highly parasitized nestlings had corticosterone concentrations twice as high on average (42.9 ng/ml) than non-parasitized nestlings (20.2 ng/ml). Telomeres of highly parasitized female nestlings significantly shortened as eagles aged, but we found no effect of parasitism on the telomeres of male nestlings. Finally, in nests with higher infestation levels, eagle nestlings were 20 times more likely to die, often because they left the nest before they could fly. These results suggest that H. inodorus may limit local golden eagle populations by decreasing productivity. For eagles that survived infestation, chronically elevated glucocorticoids and shortened telomeres may adversely affect cognitive function or survival in this otherwise long-lived species. Emerging threats from ectoparasites should be an important management consideration for protected species, like golden eagles.
Assessment of no-reflow phenomenon by non-constrast computed tomography in patients with acute myocardial infarction undergoing primary percutaneous coronary angioplasty
Authors: Vallejo E , Cardosa D , Rangel A
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

  Coronary no-reflow phenomenon after primary percutaneous coronary angioplasty (pPCI) is an independent predictor of adverse clinical outcomes after AMI regardless of infarct size. The incidence of no-reflow varies widely depending on the diagnostic methods used.

 

Purpose

Showing whether non-contrast CT performed after pPCI might be usefull as a diagnosis of no-reflow phenomenon.

Methods

Six STEMI patients (mean age = 68.3 y/o) underwent revascularization by pPCI and stent placement within 6 hours after onset of angina and within less than 90 minutes of door-to-balloon time.  Due to the outbreak of SARS-Cov-2, chest CT scanning was indicated in all patients before coronary unit admission (192 ± 102 mins after pPCI).  

Results

  Three patients with a higher time than the mean angina time and than the mean door-to-ballon time (190 ± 149.3 versus 170 ± 107.5 and 63 ± 6.08 vs 56 ± 11.5, respectively) developed an interventional type of no-reflow phenomenon (Table 1) and CT scanning showed regional myocardial contrast retention related to the culprit coronary artery (Figure 1).  On the other hand, three patients with a lower time than the mean angina time and than the mean door-to-ballon time showed TIMI III flow after pPCI (Table 1) and CT scanning showed no regional myocardial contrast retention (Figure 2). 

Conclusion

Myocardial regional contrast retention, evaluated by non-contrast and non-ECG-gated computed tomography after pPCI, might be usefull for no-reflow diagnosis.

TABLE 1

AGE ANGINA-TIME DOOR-TO-BALLON-TIME  BASAL/cTnT  POST-pPCI/cTnT  CHANGE/cTnT

PTS 68 ± 17y/o 170 ± 107mins 56 ± 11mins 1635 ± 2549ng/L 9621 ± 4586ng/L 588% 

(N = 6)

NO-REFLOW

PATS 65 ± 25y/o 190 ± 149mins 63 ± 6mins 761 ± 837ng/L 11151 ± 2787ng/L 1465%

(N = 3)

TIMI-III FLOW

PTS 72 ± 9y/o 117 ± 76mins 49 ± 12mins 2219 ± 3653ng/L 18091 ± 6148ng/L 364%

(N = 3)
Prevalence of coronary artery calcification in young adults in UK
Authors: Koulaouzidis G
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Coronary atherosclerosis is a continuous process beginning early in life, with a long and clinically asymptomatic phase, before manifestations appear in middle and/or late adulthood. Coronary artery calcification (CAC) is a well-established marker of atherosclerosis; but the clinical validity of CAC in young adults (traditionally considered as a population group of low cardiovascular risk) remains unclear.

Aim

We aimed to assess the prevalence of CAC in a population of young individuals without previous history of coronary artery disease (CAD) in the UK and its association with conventional cardiovascular risk factors.

Methods

This analysis includes 4186 asymptomatic young individuals who underwent electron beam computed tomography (EBCT). Demographic information and the presence of cardiovascular risk factors were abstracted from referral letters and/or questionnaires completed by the patients prior to their tests. Individuals with previously documented CAD or chronic kidney disease were excluded. All EBCT CAC studies were performed using the same scanner (Imatron C300 Ultrafast computed tomography scanner, GE Healthcare, London, UK) and the same scanning protocol.

Results

The age (mean SD) of the study cohort was 40.5 ±3.6 years (range 26–45 years, 83.8% males). Hypertension, dyslipidemia, and diabetes mellitus (DM) were present in 15.5, 7.9, and 2.8% of individuals, respectively. Family history of premature CAD was present in 17% and 17.4% were smokers. 

CAC was present in 21.8% of the cohort, while individuals with CAC comparing with those with CAC score 0 were males (95.2 vs. 80%, p < 0.002), older in age (41.4 3.2 vs. 40.3 3.7 years, p < 0.0001), with DM (5.5 vs. 25%, p < 0.0001), hypertension (22 vs. 13.7%, p < 0.0001), and dyslipidemia (14.8 vs. 6%, p < 0.0001). The prevalence of CAC score 0, 1–100, 101–400, 401–1000, >1000 were 78.2, 19, 2.1, 0.5, and 0.2%, respectively. The prevalence and distribution of CAC among various age groups are shown in Table 1. CAC was found in 24.8% of males (CAC score 1–100, 101–400, 400–1000, >1000 in 21.6, 2.5, 0.5, and 0.1%, respectively) and 6.6% of females (CAC score 1–100, 101–400, 400–1000, >1000 in 5.4, 0.6, 0.15 and 0.4%, respectively) (p < 0.0001). There was no statistical difference of mean CAC score between genders (males 13.8 72.7; females 11.8 142.4; p = 0.6). In multivariate analysis, the presence of CAC was associated with age (p< 0.0001), male gender (p< 0.0001), DM (p< 0.0001), hypertension (p< 0.0001), and dyslipidemia (p< 0.0001). 

Conclusion

  In a large cohort of asymptomatic young individuals, subclinical atherosclerosis (CAC score >0) was identified in approximately 20%. Assessment of CAC score is a useful clinical tool in young individuals, as it can confirm the presence of subclinical atherosclerosis.
Evaluation of visual and quantitative parameters of MPS SPECT in MINOCA patients in one year after acute coronary syndrome: comparison with CMR
Authors: Mochula A , Mochula O , Maltseva A , Vorobyeva D , Ryabov V , Zavadovskiy K
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background. In recent years a group of patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA) is of interest. In this group of patients, there is a lack of information related to myocardial perfusion, blood flow and reserve, which could be important in term of risk and prognosis assessment.

Purpose. To assess the visual and quantitative MPS SPECT parameters in MINOCA patients compared to cardiac magnetic resonance (CMR) data.

Methods.  In the period from 2017 to 2018 were examined 18 (8 male, mean 62.9 ± 10.7years) consecutive patients with acute myocardial infarction without obstructive coronary artery disease (MINOCA). Within 7-10 days after admission to the hospital and one year later all patients underwent SPECT myocardial perfusion scintigraphy (MPS) with the assessment of standard indices (SSS, SRS, SDS) and quantitative parameters: rest MBF (rMBF), stress MBF (sMBF) and CFR (on CZT gamma-camera). Also, all patients underwent CMR. Based on CMR data all patient were divided into two groups: 1) patients with non-ischemic type of injury and 2) patients with ischemic type of injury.

Results. We found out significant correlation between regional quantitative SPECT indices and transmural extent of myocardial infarction evaluated by CMR: r=–0.4 for sMBF; r=–0.35 for CFR (p < 0.05).

In the first hospitalization this groups of patient didn`t have of any differences, according visual and quantitative data by SPECT. However, in one year, visual analysis showed that SSS and SDS were significantly (p < 0.001) lower in patient with ischemic type of injury by CMR data: 2 (2; 3) vs 5.5 (4; 9) and 2 (1; 3) vs 4.5 (2; 5), respectively. According to the quantitative MPS data analysis, global and CFR values were significantly lower in patients with non-ischemic type of injury 1.30 (1.14; 1.75) vs 1.71 (1.34; 1.81).

Conclusion. The analysis of quantitative MPS SPECT parameters showed that such approach allows identifying MBF and CFR disturbances. These results showed that MINOCA patients are heterogeneous group and require more strong investigation, observation and treatment.
Myocardial perfusion scintigraphy during the COVID-19 pandemic - findings from the university teaching hospital in Slovenia
Authors: Guzic Salobir B , Dolenc Novak M , Stalc M
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Department for nuclear medicine in the University medical centre Ljubljana provides nuclear medicine diagnostic procedures for approximately 1.000.000 inhabitants of Slovenia. As many countries in Europe, Slovenia was faced with the first wave of the COVID-19 pandemic in early spring of 2020. Since our country is situated next to the northern part of Italy, where the situation was critical, our Ministry of health issued specific recommendations in March 2020. The aim was to increase hospital capacities for COVID-19 patients through limiting non-urgent diagnostic tests including myocardial perfusion scintigraphy (MPS) and to minimize the spread of the virus into hospital departments. The epidemiologic situation of the first wave resolved within 3 months. In the second wave of the pandemic in autumn 2020, the recommendations on patient care in non COVID-19 cases were less limiting to avoid worsening of non COVID-19 related diseases and patient prognosis.

Purpose

The aim of our study was to evaluate the influence of the COVID-19 pandemic on MPS in our medical institution.

Methods

Data on numbers of MPS, clinical characteristics of the patients and findings of MPS were prospectively collected for the first wave (in spring from March 15th to June 15th 2020) and second wave (in autumn from September 15th to December 15th 2020) of the pandemic and were compared with the same periods in 2019. 

Results

During the first wave we performed 40% less MPS, significantly more patients had pharmacological stress and were outpatients than in spring 2019. There were no significant differences in other clinical characteristics and MPS findings (Table 1 and Figure 1). In autumn 2020 we reorganized our schedule to increase the number of patients, which was once again comparable to previous year’s autumn. Although the number of patients was comparable, patients were now significantly older and had more often pharmacological stress, but there were no significant differences in other clinical data or MPS findings (Table 1 and Figure 1).

Conclusions

In our hospital, during the first wave of COVID-19 pandemic, we performed significantly less MPS than in the same period of the previous year. To minimize the possibility of virus transmission from asymptomatic patients, we followed international recommendations and avoided exercise stress tests but increased the percentage of pharmacological stress tests. A similar approach regarding the type of stress tests was chosen for the second wave in autumn of 2020. However, we decided to increase the number of MPS performed, in order to lessen the negative impact of the pandemic on non COVID-19 related diseases, focusing on coronary artery disease.
The use of SPECT/CT quantification of 99mTc-PYP uptake to assess tafamidis treatment response in ATTR cardiac amyloidosis
Authors: Elsadany M , Godoy Rivas C , Arora S , Jaiswal A , Weissler-Snir A , Duvall WL
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background/Introduction

Nuclear scintigraphy with bone-avid radiotracers such as Tc-99m-PYP, Tc99m-DPC and Tc-99m-HMDP are used to diagnose transthyretin (ATTR) cardiac amyloidosis with limited quantification employing a semi-quantitative visual score and a heart to contralateral lung ratio. Therapy for ATTR cardiac amyloid currently is limited to a single FDA approved agent, tafamidis, however, there is no data regarding the longitudinal assessment of imaging findings in patients undergoing therapy. SPECT/CT acquisition and analysis with dedicated software can provide volumetric assessment and quantification of cardiac tracer uptake.

Purpose

The purpose of this study was to perform longitudinal assessment of cardiac ATTR amyloid 99mTc-PYP imaging findings to determine if treatment with tafamidis results in any change in quantitative measures of tracer uptake. There is no data on if treatment results in a decrease in cardiac amyloid burden as assessed by 99mTc-PYP imaging.

Methods

A prospective, single center, study of patients with ATTR cardiac amyloid being treated with tafamidis (either 80mg or 61mg dose) who have baseline and follow-up 99mTc-PYP studies. SPECT/CT quantification software was used to quantify heart, lung, and bone tracer uptake and generate standardized uptake values (SUVs). Comparison of baseline (before treatment) total SUVs, mean SUV value, percentage of the injected dose, mean SUV of heart to mean SUV of bone ratio and to mean SUV of right lung ratio was made to the values obtained at follow-up after tafamidis treatment. Measurements were obtained from the whole heart and the isolated left ventricle. Data was obtained by two physicians and the results averaged.

Results

5 patients were analyzed with a mean age 73.8 ± 7.7, 80% were males, and a mean length of tafamidis therapy at repeat imaging of 12.5 ± 3.8 months. At follow-up there was an average decrease in whole heart total SUV counts by -25.9 ± 10.3%, in the mean SUV value by -18.2 ± 18.2% and in the percentage of injected dose by -23.7 ± 14.0%. Similar decreases were seen in the isolated left ventricle measures. Heart to bone and heart to lung ratios showed a mixed response to therapy. Detailed results are provided in the table.

Conclusion

The measurements of total SUV counts, mean SUV value, and percentage of the injected dose showed improvement with tafamidis treatment. The ratios did not uniformly show improvement and the reason for this finding is unclear. This new technique offers a potential method for following tafamidis therapy and assessing the cardiac amyloid burden.
Influence of adenosine and regadenoson on left ventricular ejection fraction, myocardial blood flow and hemodynamics in vasodilator 82-Rubidium PET
Authors: Frey S , Honegger U , Clerc OF , Caobelli F , Haaf PH , Zellweger MJ
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Most 82Rubidium-(Rb)-Positron emission tomography (PET) studies for myocardial perfusion, dipyridamole was used as vasodilator. Less data is available for adenosine and regadenoson.

Purpose

Therefore, the aim was to evaluate the influence of adenosine and regadenoson on left ventricular ejection fraction (LVEF), myocardial blood flow (MBF) and hemodynamics in vasodilator 82Rb-PET.

Methods

Consecutive patients (n = 2299) with suspected or known coronary artery disease (CAD) undergoing 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (abnormal defined as summed stress score ≥4). Differences between stress and rest values (LVEF, MBF, hemodynamics) were calculated. The threshold of stress LVEF able to exclude a relevant ischemia (as defined by ≥10% myocardium ischemic based on SDS score) was assessed.

Results

Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with suspected CAD, rest/stress LVEF were 68 ± 12% and 73 ± 12% (p < 0.001), in patients with prior CAD 60 ± 14% and 63 ± 15% (p < 0.001). LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (p < 0.001). Global rest MBF (rMBF), stress MBF (sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in suspected CAD patients compared to prior CAD patients (1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, p < 0.001), and in normal versus abnormal scans, irrespective of CAD status (no CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; known CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, p < 0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia with a negative predictive value (NPV) of 94% (CI 92-95%).

Conclusions

Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared with normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.
Entropy-based myocardial blood flow measurements using PET: a way to improve reproducibility
Authors: Van Dalen J , Koenders SS , Vendel BN , Jager PL , Van Dijk JD
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background and purpose

Myocardial blood flow (MBF) measurements using PET are increasingly used to guide the management of patients with (suspected) coronary artery disease (CAD). Day-to-day variability of these measurements is poor with a 21% standard deviation or 40% 95%-confidence interval [Reference: JACC Cardiovasc Imaging, 2017;10(5):565]. This limits clinical applicability in diagnosis, risk stratification and follow-up as these all depend on comparison of flow values with fixed cut-off values. We expect that reproducibility can be improved by combining flow measurements with the variation of flow values within the myocardium. As entropy is a measure of variability of the associated distribution, we compared the reproducibility of an entropy-based flow parameter with that of conventional myocardial flow reserve (MFR) measurements.

Methods

We performed a study using intra-individual comparison in 24 patients who underwent rest and regadenoson-induced stress myocardial perfusion imaging using Rubidium-82 on two different PET systems (PET1: Discovery 690, GE Healthcare, and PET2: Vereos, Philips Healthcare) within 3 weeks. MBF for both rest and stress was calculated using Lortie’s one-tissue compartment model (Corridor4DM, INVIA). MFR (ratio of MBF stress/rest) was determined for the myocardial as a whole (MFRglobal), for the three vascular territories: LAD, LCX and RCA (MFRregional) and for the 17 segments. Next, we calculated Shannon’s entropy to measure the variation of the 17 MFR segmental values. We multiplied Shannon’s entropy by the mean of the MFR segmental values resulting in an entropy-based MFR (MFRentropy). For each patient MFRglobal, MFRregional and MRFentropy were compared between both PET systems. For each of the three parameters the test-retest precision was calculated as the SD of the relative difference between measurements.

Results

The mean difference in MFR measurements between both cameras did not differ from zero (p > 0.05). Mean values for PET1 were MFRglobal = 2.4, MFRregional = 2.4 (LAD), 2.4 (LCX) and 2.5 (RCA), and MFRentropy = 2.4. For PET2 we found MFRglobal = 2.5, MFRregional = 2.5 (LAD), 2.4 (LCX) and 2.6 (RCA), and MFRentropy = 2.5. Test-retest precision was lower for MFRentropy with 11% compared to that of MFRglobal (21%), MFRregional LAD (22%), MFRregional LCX (23%) and MFRregional RCA (24%) (p < 0.01).

Conclusion

The reproducibility of myocardial flow reserve measurements using Rubidium-82 PET improved by a factor of 2 when an entropy-based flow parameter instead of global or regional MFR parameters is used. This entropy-based flow-parameter may be used to better discriminate ischemia from non-ischemia and may therefore improve CAD management.
Prognostic value of left ventricular ventricular dyssynchrony in left bundle branch block patients
Authors: Cortes C , Aramayo G EN , Barboza PE , Claros EM , Embon MA
Published: July 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Patients with left bundle branch block (LBBB) patterns on the electrocardiogram include a heterogeneous group of patients with different prognosis and some of them with or without left ventricular mechanical dyssynchrony (LVMD). LVMD obtained by gated technetium 99m single photon emission computed tomography (SPECT) imaging could be an early tool to detect myocardial damage, identifying a high risk group.

Purpose

The aim of this study was to assess the prognostic value of LVMD in LBBB patients.

Methods

Five hundred and eighty consecutive patients with LBBB were referred for gated SPECT from August 2011 to June 2019. Phase analysis parameters Standard deviation (SD) and histogram bandwidth (HB) were obtained in rest gated SPECT imaging. LVMD was defined as the upper limit of the highest normal for phase analysis results in our control patients mean values plus two standard deviations (SD ≥ 21° or HB ≥ 67°). Follow up was performed by telephone contact or medical history review. Hard endpoint was all-cause death. Event-free survival curves were obtained. Univariate and multivariate regression analysis were performed.

Results

LVMD was observed in 254 (44%) patients. Compared to non LVMD patients had: similar age (67.68 ± 11.01 vs. 67.2 ± 10.3 y; p NS), more male (75.2% vs 39.6%), more hypertension (75.2% vs. 66.8%), more diabetes (22.8% vs. 13%) and more smoking history (31.9% vs. 23.7%) all p <0.05. A total of 495 patients completed the follow up (mean 29.8 ± 25.8 months). Fourteen patients died (2.8%), 12 had LVMD. Fig 1 shows Kaplan-Meier curve of event-free survival in relation to LVMD. Variables associated with all-cause death in the univariate analysis were: Score Rest Summed ≥ 4 (p 0.02), LV ejection fraction ≤ 35% (p < 0.01), diabetes (p 0.03) and LVMD (p <0.01). The absence of LVMD was a predictor of the lower risk of all-cause death in the multivariate analysis (adjusted hazard ratio: 0.13, 95% confidence interval: 0.03- 0.56; p < 0.01).

Conclusion

In our population of patients with LBBB, the absence of LVMD assessed by gated SPECT imaging identifies patients with lower risk of hard adverse events.
Fontan operation at less than 3 years of age is not a risk factor for long-term failure
Authors: Cao Jacob Y , Marathe Supreet P , Zannino Diana , Celermajer David S , Justo Robert N , Alphonso Nelson , d’Udekem Yves , Winlaw David S
Published: July 2021

OBJECTIVES

The age at which the Fontan operation is performed varies globally. Over the last decade, the median age of patients having the Fontan in Australia and New Zealand has been 4.6 years, including 6% of patients younger than 3 years. Long-term outcomes of an early Fontan operation are unclear and are described in this study.

METHODS

Patients from the Australian and New Zealand Fontan Registry were grouped by age at Fontan. A Fontan before 3 years (early Fontan) was compared to the combined second and third quartiles by age at surgery in the Registry (3.6–6.1 years; control). Outcomes included Fontan failure (death, transplant, New York Heart Association functional group III/IV heart failure, Fontan takedown or conversion, protein losing enteropathy and plastic bronchitis), arrhythmias, thromboembolism and reinterventions.

RESULTS

A total of 191 patients who had early Fontan operations were compared to 781 controls. Profound or progressive cyanosis was noted more frequently in the early than in the control group (63% vs 23%; P < 0.001). The early group was followed up for a median 22.1 years. The incidence of long-term failure was similar between the 2 groups (early, 1.08 failures per 100 patient-years of follow-up vs control, 0.99; log-rank P = 0.79). Adjusted for risk factors, early age at Fontan was not a risk factor for long-term failure [hazard ratio (HR) 1.16, 95% confidence interval (CI) 0.77–1.76; P = 0.48], new-onset arrhythmia (HR 0.93, 95% CI 0.63–1.39; P = 0.73), thromboembolism (HR 0.50, 95% CI 0.28–0.91; P = 0.024) or reintervention (HR 1.08, 95% CI 0.80–1.45; P = 0.62).

CONCLUSIONS

Having the Fontan operation at an early age was not a risk factor for short- or long-term adverse outcomes in our cohort.
Harvest strategies for climate-resilient fisheries
Authors: Collie Jeremy S , Bell Richard J , Collie Samuel B , Minto Cóilín
Published: July 2021

A pressing challenge for climate-vulnerable fisheries is how to manage now for present and future climate change. In contrast to climate forecasting approaches, we track integrated signals of change for example populations in a climatically forced region and use stochastic dynamic programming to compare the performance of a range of management-ready policies over all possible future states. Our main results highlight: (i) that biomass-linked harvest control rules (HCRs) can partially compensate for changing production, even if the HCR is time invariant; and (ii) that the form of utility (e.g. risk neutral or risk averse) can result in remarkably different optimal decision paths. Performance over future horizons degrades marginally from dynamic HCRs to static HCRs (except at low productivity where differences are more pronounced) but markedly when the biomass level is ignored altogether, as is the case in many managed fish populations globally. Understanding the processes whereby climate affects productivity is important for interpreting past data, but forecasts are not needed for tactical decision making now. Instead, we argue that the priorities for managing fish stocks influenced by climate change are to: measure the current productivity, assess the current abundance of the stock, and respond with a dynamic HCR.
Surgical treatment of a 36-year-old patient with asphyxiating thoracic dysplasia
Authors: Wang Wenlin
Published: July 2021

Asphyxiating thoracic dysplasia is a rare and dangerous genetic disease. Many children with this disease die early in life of severe hypoxia, and it is extremely rare that they survive to adulthood. We recently treated a 36-year-old patient who had asphyxiating thoracic dysplasia with a special surgical method and achieved satisfactory results. A review of the literature showed that this patient is the oldest surviving person with this condition.
Finite element approximation of fractional Neumann problems
Authors: Bersetche Francisco M , Borthagaray Juan Pablo
Published: July 2021

In this paper, we consider approximations of Neumann problems for the integral fractional Laplacian by continuous, piecewise linear finite elements. We analyze the weak formulation of such problems, including their well-posedness and asymptotic behavior of solutions. We address the convergence of the finite element discretizations and discuss the implementation of the method. Finally, we present several numerical experiments in one- and two-dimensional domains that illustrate the method’s performance as well as certain properties of solutions.