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Purpose Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [18F]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism. Methods Twenty-five men with newly diagnosed treatment-naïve metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [18F]PSMA-1007 PET/CT immediately before and 3–4 weeks after ADT initiation (degarelix). Before ADT, [18F]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as ΔSUVmax. Results All the patients reached castration levels of testosterone at the time of the second [18F]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (≥ 20%) in PSMA uptake, with a median ΔSUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [18F]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA ΔSUVmax and FDG SUVmax (p p Conclusions A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive. Trial registration NCT03876912, registered 15 March 2019.

Background Our aim was to investigate the discriminative value of 18F-Flutemetamol PET in longitudinal assessment of amyloid beta accumulation in amnestic mild cognitive impairment (aMCI) patients, in relation to longitudinal cognitive changes. Methods We investigated the change in 18F-Flutemetamol uptake and cognitive impairment in aMCI patients over time up to 3 years which enabled us to investigate possible association between changes in brain amyloid load and cognition over time. Thirty-four patients with aMCI (mean age 73.4 years, SD 6.6) were examined with 18F-Flutemetamol PET scan, brain MRI and cognitive tests at baseline and after 3-year follow-up or earlier if the patient had converted to Alzheimer´s disease (AD). 18F-Flutemetamol data were analyzed both with automated region-of-interest analysis and voxel-based statistical parametric mapping. Results 18F-flutemetamol uptake increased during the follow-up, and the increase was significantly higher in patients who were amyloid positive at baseline as compared to the amyloid-negative ones. At follow-up, there was a significant association between 18F-Flutemetamol uptake and MMSE, logical memory I (immediate recall), logical memory II (delayed recall) and verbal fluency. An association was seen between the increase in 18F-Flutemetamol uptake and decline in MMSE and logical memory I scores. Conclusions In the early phase of aMCI, presence of amyloid pathology at baseline strongly predicted amyloid accumulation during follow-up, which was further paralleled by cognitive declines. Inversely, some of our patients remained amyloid negative also at the end of the study without significant change in 18F-Flutemetamol uptake or cognition. Future studies with longer follow-up are needed to distinguish whether the underlying pathophysiology of aMCI in such patients is other than AD.

Brown adipose tissue (BAT) thermogenesis is activated by feeding. Recently, we revealed a secretin-mediated gut-BAT-brain axis, which stimulates satiation in mice, but the purpose of meal-induced BAT activation in humans has been unclear. In this placebo-controlled, randomized crossover study, we investigated the effects of intravenous secretin on BAT metabolism (measured with [18F]FDG and [15O]H2O positron emission tomography) and appetite (measured with functional magnetic resonance imaging) in healthy, normal weight men (GUTBAT trial no. NCT03290846). Participants were blinded to the intervention. Secretin increased BAT glucose uptake (primary endpoint) compared to placebo by 57% (median (interquartile range, IQR), 0.82 (0.77) versus 0.59 (0.53) μmol per 100 g per min, 95% confidence interval (CI) (0.09, 0.89), P = 0.002, effect size r = 0.570), while BAT perfusion remained unchanged (mean (s.d.) 4.73 (1.82) versus 6.14 (3.05) ml per 100 g per min, 95%CI (-2.91, 0.07), P = 0.063, effect size d = -0.549) (n = 15). Whole body energy expenditure increased by 2% (P = 0.011) (n = 15). Secretin attenuated blood-oxygen level-dependent activity (primary endpoint) in brain reward circuits during food cue tasks (significance level false discovery rate corrected at P = 0.05) (n = 14). Caloric intake did not significantly change, but motivation to refeed after a meal was delayed by 39 min (P = 0.039) (n = 14). No adverse effects were detected. Here we show in humans that secretin activates BAT, reduces central responses to appetizing food and delays the motivation to refeed after a meal. This suggests that meal-induced, secretin-mediated BAT activation is relevant in the control of food intake in humans. As obesity is increasing worldwide, this appetite regulating axis offers new possibilities for clinical research in treating obesity.

Background and Objective The newer adenosine diphosphate (ADP) receptor blockers ticagrelor and prasugrel are superior to clopidogrel in the long-term management of acute coronary syndrome (ACS). We evaluated the acute performance (prehospital loading) of these ADP receptor blockers in a primary percutaneous coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Methods In a retrospective, single-center registry study, data on all STEMI patients admitted for their first primary PCI between January 2007 and April 2020 were analyzed (n = 3218). The three ADP receptor blockers were mainly used during consecutive periods (clopidogrel 2007–2010, prasugrel 2011–2014, and ticagrelor 2014–2020), and were compared with risk factor-adjusted multivariate logistic regression for acute 3- and 7-day mortality and culprit artery flow before and after PCI. Results Of the 3218 total patients, 47.6% (n = 1532) were treated with ticagrelor, 22.1% (n = 711) were treated with prasugrel, and 30.3% (n = 975) were treated with clopidogrel. The use of ticagrelor or prasugrel as opposed to clopidogrel was associated with better culprit artery flow before PCI (odds ratio [OR] 1.21 for moderate or good flow, 95% confidence interval [CI] 1.03–1.42, p = 0.022), as well as lower acute mortality (OR 0.66 for 3-day mortality, 95% CI 0.46–0.95, p = 0.025; and OR 0.71 for 7-day mortality, 95% CI 0.52–0.98, p = 0.039). The results in regard to acute mortality were highlighted among patients with short treatment delays (disappearing with longer treatment delays; p

We present an updated global analysis of collinearly factorized nuclear parton distribution functions (PDFs) at next-to-leading order in perturbative QCD. In comparison to our previous fit, EPPS16, the present analysis includes more data from proton-lead collisions at the Large Hadron Collider: 5TeV double-differential CMS dijet and LHCb D-meson data, as well as 8TeV CMS W$^\pm$ data. These new data lead to significantly better-constrained gluon distributions at small and intermediate values of the momentum fraction $x$, confirming the presence of shadowing and antishadowing for gluons in large nuclei. In addition, we include Jefferson Lab measurements of deeply inelastic scattering which probe nuclear PDFs at large $x$ and low virtualities. For the first time within the Hessian framework, we now also explore the uncertainties of nuclear PDFs due to the errors in the baseline proton PDFs. We release the results of our analysis as a new public parametrization of nuclear PDFs called EPPS21., Minor changes to match the published version

We examined Indonesian school teachers’ perceptions and expectations about their professional learning, and their justifications for these, before they embarked on a transnational master’s programme carried out in both Indonesia and Finland. The data were collected using the method of empathy-based stories. The findings showed that the teachers expected the programme content, execution and internationality to impact positively on their professional learning, while negative professional learning scenarios were framed as stemming from a lack of personal motivation or lack of support from the Indonesian community. Moreover, the teachers expected to become more skilled professionals not only as teachers in their classrooms but also more widely as experts in their communities.

Background There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis. Methods In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality. Results A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.5 ± 2.2% vs. SAVR 3.5 ± 2.8%, p = 0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p = 0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4 years was 13.9% in the TAVR group and 6.9% in the SAVR group (p = 0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p = 0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts. Conclusions The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome. Trial registration ClinicalTrials.gov Identifier: NCT03385915.

The diagnostic imaging techniques currently used to evaluate the arterial atherosclerosis hinge on the manual marking and calculation of the stenosis degree. However, the manual assessment is highly dependent on the operator and characterized by low replicability. The study aimed to develop a fully-automated tool for the segmentation and analysis of atherosclerosis in the extracranial carotid arteries. The dataset consisted of 59 randomly-chosen individuals who had undergone head-and-neck computed tomography angiography (CTA), at the Tampere University Hospital, Tampere, Finland. The analysis algorithm was mainly based on the detection of carotid arteries, delineation of the vascular wall, and extraction of the atherosclerotic plaque. To improve the vascular detection rate, the model-based and volume-wide analytical approaches were deployed. A new fully-automated vascular imaging (VASIM) software tool was developed. For stenosis over 50%, the success rate was 83% for the detection and segmentation. Specificity and sensitivity of the algorithm were 25% and 83%, respectively. The overall accuracy was 71%. The VASIM tool is the first published approach for the fully-automated analysis of atherosclerosis in extracranial carotid arteries. The tool provides new outputs, which may help with the quantitative and qualitative, clinical evaluation of the atherosclerosis burden and evolution. The findings from this study provide a basis for the further development of automated atherosclerosis diagnosis and plaque analysis with CTA.

Microalgal cultivation in aquaculture wastewater (AWW) from recirculating aquaculture systems (RAS) is an approach for combined production of valuable algal biomass and AWW treatment. The growth, nutrient uptake, fatty acid (FA) profile, and tocopherol content of mixed algal cultures of Euglena gracilis with Selenastrum grown in AWWs from pikeperch (Sander lucioperca) and catfish (Clarias anguillaris) RAS were studied. The highest algal biomass (1.5gL(-1)), lipid (84.9mgL(-1)), and tocopherol (877.2gL(-1)) yields were achieved in sludge-amended pike perch AWW. Nutrient removal rates in experiments were 98.9-99.5 and 98.4-99.8% for NH4-N and PO4-P, and 75.4-89.2% and 84.3-95.7% for TN and TP, respectively, whereas the COD was reduced by 45.8-67.6%. Biomass EPA and DHA content met, while ARA and tocopherol content exceeded the requirements for fish feed. Algal cultivation in AWWs is a promising alternative for AWW treatment while providing a replacement for fish oil in feed.

The purpose of this study was to evaluate 18F-FACBC PET/CT, PET/MRI, and multiparametric MRI (mpMRI) in detection of primary prostate cancer (PCa). Twenty-six men with histologically confirmed PCa underwent PET/CT immediately after injection of 369 ± 10 MBq 18F-FACBC (fluciclovine) followed by PET/MRI started 55 ± 7 min from injection. Maximum standardized uptake values (SUVmax) were measured for both hybrid PET acquisitions. A separate mpMRI was acquired within a week of the PET scans. Logan plots were used to calculate volume of distribution (VT). The presence of PCa was estimated in 12 regions with radical prostatectomy findings as ground truth. For each imaging modality, area under the curve (AUC) for detection of PCa was determined to predict diagnostic performance. The clinical trial registration number is NCT02002455. In the visual analysis, 164/312 (53%) regions contained PCa, and 41 tumor foci were identified. PET/CT demonstrated the highest sensitivity at 87% while its specificity was low at 56%. The AUC of both PET/MRI and mpMRI significantly (p 3 + 4 tumors were significantly (p

There is a substantial interest in the development of NK1 substance P antagonists as potential treatments for various neuropsychiatric and somatic disorders. The aim of this study was to determine whether [18F]SPA-RQ can be utilized as a tool for studying the whole body distribution and function of NK1 receptors in preclinical settings. The compound was injected into guinea pigs with or without premedication with a NK1 receptor antagonist (NK1A-2). For comparison, we included two rats in the study, as the affinity of antagonists for NK1 receptors is known to vary between species. The whole body biodistribution of the tracer was determined at several time points. The tracer showed specific binding in organs compatible with the known location of NK1-receptors. Premedication with a NK1 antagonist led to an inhibited uptake of [18F]SPA-RQ in several organs of guinea pigs, notably intestine, pancreas, urinary bladder, uterus, skin and lung. Specific binding was also seen in both cortex and striatum. In contrast, negligible specific binding was observed in the rat brain with [18F]SPA-RQ, whereas the tracer uptake in peripheral tissues was similar to that seen in guinea pigs. We conclude that [18F]SPA-RQ/PET is a useful tool to study the distribution and function of peripherally located NK1 receptors e.g. in different disease models.

Back-translation of clinical imaging biomarkers of Alzheimer’s disease (AD), such as alterations in cerebral glucose metabolism detected by [18F]FDG positron emission tomography (PET), would be valuable for preclinical studies evaluating new disease-modifying drugs for AD. However, previous confounding results have been difficult to interpret due to differences in mouse models and imaging protocols between studies. We used an equivalent study design and [18F]FDG µPET imaging protocol to compare changes in cerebral glucose metabolism in commercial transgenic APPSwe-PS1dE9 (n = 12), Tg2576 (n = 15), and wild-type mice (n = 15 and 9). Dynamic [18F]FDG scans were performed in young (6 months) and aged (12 or 17 months) mice and the results verified by ex vivo methods (i.e., tissue counting, digital autoradiography, and beta-amyloid and Iba-1 immunohistochemistry). [18F]FDG uptake exhibited significant regional differences between genotypes (TG Swe-PS1dE9 model, whereas similar differences were not present in Tg2576 mice. In both models, only weak correlations were detected between regional beta-amyloid deposition or microgliosis and [18F]FDG uptake. By using equivalent methodology, this study demonstrated differences in cerebral glucose metabolism dysfunction detected with [18F]FDG PET between two widely used commercial AD mouse models.

The aim of this study was to explore the association between liver, mediastinum and tumor 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) uptake during chemotherapy in diffuse large B cell lymphoma (DLBCL). Nineteen patients with proven DLBCL underwent positron emission tomography (PET)/X-ray computed tomography scan at baseline, 1 week and 2 cycles after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy, and again after chemotherapy completion. The mean and maximal standardized uptake value (SUVmean and SUVmax) of the liver and mediastinum were measured and correlated with the tumor SUVmax, SUVsum, whole-body metabolic tumor volume (MTVwb), and total lesion glycolysis (TLG). At baseline, both the liver and mediastinum SUVmean and SUVmax correlated inversely with the tumor MTVwb or TLG (p

Atherosclerosis is one of the leading causes of mortality in the western world. Computed tomography angiography (CTA) is the conventional imaging method used for pre-surgery assessment of the blood flow within the carotid vessel. In this paper, we present a proof of concept of a novel, fast and operator independent protocol for the automatic detection (seeding) of the carotid arteries in CTA in the thorax and upper neck region. The dataset is composed of 14 patients' CTA images of the neck region. The performance of this method is compared with manual seeding by four trained operators. Inter-operator variation is also assessed based on the dataset. The minimum, average and maximum coefficient of variation among the operators was (0, 2, 5 %), respectively. The performance of our method is comparable with the state of the art alternative, presenting a detection rate of 75 and 71 % for the lowest and uppermost image levels, respectively. The mean processing time is 167 s per patient versus 386 s for manual seeding. There are no significant differences between the manual and automatic seed positions in the volumes (p = 0.29). A fast, operator independent protocol was developed for the automatic detection of carotid arteries in CTA. The results are encouraging and provide the basis for the creation of automatic detection and analysis tools for carotid arteries.

A statistical analysis of data from ultra-relativistic heavy-ion collisions has uncovered the specific viscosities of the quark–gluon plasma — suggesting that the hottest matter in the current Universe behaves like a near-perfect fluid.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p

Purpose In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour’s biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [18F]FDG, a new hypoxia tracer [18F]EF5 and the perfusion tracer [15O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.

Obstructive sleep apnea (OSA) has been associated with an elevated rate of cardiovascular mortality. However, this issue has not been investigated in patients with elevated proneness to cardiovascular diseases. Our hypothesis was that OSA would have an especially adverse effect on the risk of cardiovascular mortality in Finnish individuals exhibiting elevated proneness for coronary heart diseases. Ambulatory polygraphic recordings from 405 men having suspected OSA were retrospectively analyzed. The patients were categorized regarding sleep disordered breathing into a normal group (apnea hypopnea index (AHI)

Purpose The aim of this study was to investigate the potential of [18F]flutemetamol as a preclinical PET tracer for imaging β-amyloid (Aβ) deposition by comparing its pharmacokinetics to those of [11C]Pittsburgh compound B ([11C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [18F]flutemetamol to Aβ deposits was studied in the Tg2576 transgenic mouse model of Alzheimer’s disease.