bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractA 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

SummaryScientists 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

Abstract
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

Abstract

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

Abstract

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 &lt; 0.002), older in age (41.4 3.2 vs. 40.3 3.7 years, p &lt; 0.0001), with DM (5.5 vs. 25%, p &lt; 0.0001), hypertension (22 vs. 13.7%, p &lt; 0.0001), and dyslipidemia (14.8 vs. 6%, p &lt; 0.0001). The prevalence of CAC score 0, 1–100, 101–400, 401–1000, &gt;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, &gt;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, &gt;1000 in 5.4, 0.6, 0.15 and 0.4%, respectively) (p &lt; 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&lt; 0.0001), male gender (p&lt; 0.0001), DM (p&lt; 0.0001), hypertension (p&lt; 0.0001), and dyslipidemia (p&lt; 0.0001).

Conclusion
In a large cohort of asymptomatic young individuals, subclinical atherosclerosis (CAC score &gt;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

Abstract

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 &lt; 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 &lt; 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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001), in patients with prior CAD 60 ± 14% and 63 ± 15% (p &lt; 0.001). LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (p &lt; 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 &lt; 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 &lt; 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

Abstract

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 &gt; 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 &lt; 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.