bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competing-risks nomogram for predicting cancer-specific death in upper tract urothelial carcinoma: a population-based analysis
Authors: Li Chengzhuo , Han Didi , Huang Qiao , Xu Fengshuo , Zheng Shuai , Li Xiang , Zhao Fanfan , Feng Xiaojie , Lyu Jun 
Published: July 2021

ObjectiveThis study aimed to use a competing-risks model to establish a nomogram to accurately analyse the prognostic factors for upper tract urothelial carcinoma (UTUC) cancer-specific death (CSD).DesignRetrospective observational cohort study.SettingThe programme has yielded a database of all patients with cancer in 18 defined geographical regions of the USA.ParticipantsWe selected patients with UTUC from the latest edition of the Surveillance, Epidemiology, and End Results database from 1975 to 2016. After excluding patients with unknown histological grade, tumour size and lymph node status, 2576 patients were finally selected.Primary and secondary outcome measuresWe used the Fine-Gray proportional subdistribution hazards model for multivariate analysis and compared the results with cause-specific hazards model. We finally constructed a nomogram for 3-year, 5-year and 8-year CSD rates and tested these rates in a validation cohort.ResultsThe proportional subdistribution hazards model showed that sex, tumour size, distant metastasis, surgery status, number of lymph nodes positive (LNP) and lymph nodes ratio (LNR) were independent prognostic factors for CSD. All significant factors associated with CSD were included in the nomogram. The 3-year, 5-year and 8-year concordance indexes were 0.719, 0.702 and 0.692 in the training cohort and 0.701, 0.675 and 0.668 in the validation cohort, respectively.ConclusionsThe competing-risks model showed that sex, tumour size, distant metastasis, surgery status, LNP and LNR were associated with CSD. The nomogram predicts the probability of CSD in patients with UTUC at 3, 5 and 8 years, which may help clinicians in predicting survival probabilities in individual patients.
Cost effectiveness of ramipril treatment for cardiovascular risk reduction
Authors: Malik I S , Bhatia V K , Kooner J S 
Published: July 2021

OBJECTIVETo assess the cost effectiveness of ramipril treatment in patients at low, medium, and high risk of cardiovascular death.DESIGNPopulation based cost effectiveness analysis from the perspective of the health care provider in the UK. Effectiveness was modelled using data from the HOPE (heart outcome prevention evaluation) trial. The life table method was used to predict mortality in a medium risk cohort, as in the HOPE trial (2.44% annual mortality), and in low and high risk groups (1% and 4.5% annual mortality, respectively).SETTINGUK population using 1998 government actuary department data.MAIN OUTCOME MEASURECost per life year gained at five years and lifetime treatment with ramipril.RESULTSCost effectiveness was £36 600, £13 600, and £4000 per life year gained at five years and £5300, £1900, and £100 per life year gained at 20 years (lifetime treatment) in low, medium, and high risk groups, respectively. Cost effectiveness at 20 years remained well below that of haemodialysis (£25 000 per life year gained) over a range of potential drug costs and savings. Treatment of the HOPE population would cost the UK National Health Service (NHS) an additional £360 million but would prevent 12 000 deaths per annum.CONCLUSIONSRamipril is cost effective treatment for cardiovascular risk reduction in patients at medium, high, and low pretreatment risk, with a cost effectiveness comparable with the use of statins. Implementation of ramipril treatment in a medium risk population would result in a major reduction in cardiovascular deaths but would increase annual NHS spending by £360 million.
Correlation between high frequency intravascular ultrasound and histomorphology in human coronary arteries
Authors: Prati F , Arbustini E , Labellarte A , Dal Bello B , Sommariva L , Mallus M T , Pagano A , Boccanelli A 
Published: July 2021

OBJECTIVETo test the efficacy of high frequency intravascular ultrasound (IVUS) transducers in identifying lipid/necrotic pools in atherosclerotic plaques.METHODS40 MHz transducers were used for in vitro IVUS assessment of 12 arterial segments (10 coronary and two carotid arteries, dissected from five different necropsy cases). IVUS acquisition was performed at 0.5 mm/s after ligature of the branching points to generate a closed system. Lipid/necrotic areas were defined by IVUS as large echolucent intraplaque areas surrounded by tissue with higher echodensity. To obtain histopathological sections corresponding to IVUS cross sections, vessels were divided into consecutive 3 mm long segments using the most distal recorded IVUS image as the starting reference. Samples were then fixed with 10% buffered formalin, processed for histopathological study, serially cut, and stained using the Movat pentacrome method.RESULTS122 sections were analysed. Lipid pools were observed by histology in 30 sections (25%). IVUS revealed the presence of lipid pools in 19 of these sections (16%; sensitivity 65%, specificity 95%).CONCLUSIONSIn vitro assessment of lipid/necrotic pools with high frequency transducers was achieved with good accuracy. This opens new perspectives for future IVUS characterisation of atherosclerotic plaques.
Increased concentrations of inflammatory mediators in unstable angina: correlation with serum troponin T
Authors: Mazzone A , De Servi S , Mazzucchelli I , Bossi I , Ottini E , Vezzoli M , Meloni F , Lotzinker M , Mariani G 
Published: July 2021

OBJECTIVETo measure plasma interferon γ, monocyte chemotactic protein-1 (MCP-1), and interleukin 6 and to assess their correlation with cardiac troponin T in unstable angina.DESIGNBlood sampling in patients undergoing coronary arteriography for known or suspected ischaemic heart disease.PATIENTS76 patients divided in three groups: 29 with unstable angina (group 1), 28 with stable angina (group 2), and 19 without ischaemic heart disease and with angiographically normal coronary arteries (group 3).MAIN OUTCOME MEASURESPlasma interleukin 6, interferon γ, MCP-1, and troponin T in the three groups of patients.RESULTSInterleukin 6 was increased in group 1 (median 2.19 (range 0.53–50.84) pg/ml) compared with the control group (1.62 (0.79–3.98) pg/ml) (p < 0.005), whereas interferon γ was higher in group 1 (range 0–5.51 pg/ml) than in the other two groups (range 0–0.74 pg/ml and 0–0.37 pg/ml; p < 0.005 and p < 0.001, respectively). Patients with unstable angina (group 1) and positive troponin T had higher concentrations of interferon γ than those with negative troponin T (0–5.51 pg/mlv 0–0.60 pg/ml, p < 0.001). Plasma MCP-1 was also higher in group 1 (median 267 (range 6–8670) pg/ml) than in the other two groups (134 (19–890) pg/ml and 84.5 (5–325) pg/ml; p < 0.005 and p < 0.001, respectively), and among group 1 patients with a positive troponin T assay than in those with normal troponin T (531 (14.5–8670) pg/mlv 69 (6–3333) pg/ml; p < 0.01). There was no difference in plasma interleukin 6 in group 1 patients between those with and without raised troponin T.CONCLUSIONSThe inflammatory cytokines interferon γ and MCP-1 are increased in patients with unstable angina, particularly in those with raised concentrations of troponin T, suggesting that they are probably related to myocardial cell damage or to plaque rupture and thrombus formation.
Management and outcome of cardiogenic shock complicating acute myocardial infarction in hospitals with and without on-site catheterisation facilities
Authors: Barbash I M , Behar S , Battler A , Hasdai D , Boyko V , Gottlieb S , Leor J 
Published: July 2021

OBJECTIVETo determine whether the availability of on-site catheterisation and revascularisation facilities influenced hospital management and outcome of patients with acute myocardial infarction complicated by cardiogenic shock.METHODSPatients with acute myocardial infarction were enrolled prospectively in four nationwide surveys during 1992, 1994, 1996, and 1998. The characteristics, management, and outcome of patients with cardiogenic shock were compared between hospitals with on-site catheterisation facilities (group 1; 18 hospitals) and without such facilities (group 2; 8 hospitals).RESULTSOf 5351 patients with acute myocardial infarction, 254 (4.7%) developed cardiogenic shock. Group 1 patients (n = 186 of 3854; 4.6%) were younger (mean (SD) age, 69.6 (12) v 73.7 (10) years, p = 0.006) and had a lower proportion of women (36% v 52%, p = 0.03) than group 2 (n = 68 of 1243; 5.2%). There was no difference in other characteristics including the use of thrombolysis. Group 1 patients more often underwent coronary angiography (26%v 4%, p < 0.001), angioplasty (21%v 4%, p = 0.002), and intra-aortic balloon counterpulsation (28% v 4%, p < 0.001). Seven day mortality was lower among group 1 than among group 2 patients (61% v 77%, p = 0.02), even after age and sex adjustment (odds ratio (OR) 0.54; 95% confidence interval (CI) 0.28 to 1.02). This outcome benefit persisted at 30 days (74%v 88%, p = 0.01; OR 0.45, 95% CI 0.18 to 0.98), and at 6 months (80% v 90%, p = 0.06; OR 0.57, 95% CI 0.22 to 1.33).CONCLUSIONSThe greater use of invasive and interventional procedures in hospitals with catheterisation facilities is associated with improved survival of patients with acute myocardial infarction complicated by cardiogenic shock. Immediate availability of invasive care facilities will improve the outcome of cardiogenic shock in the community setting.
Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population
Authors: Furuhashi M , Uno K , Tsuchihashi K , Nagahara D , Hyakukoku M , Ohtomo T , Satoh S , Nishimiya T , Shimamoto K 
Published: July 2021

OBJECTIVETo examine the modality and morbidity of asymptomatic ST segment elevation in leads V1 to V3 with right bundle branch block (Brugada-type ST shift).METHODS8612 Japanese subjects (5987 men and 2625 women, mean age 49.2 years) who underwent a health check up in 1997 were investigated. Those with Brugada-type ST shift underwent the following further examinations over a two year period after the initial check up: ECG, echocardiogram, 24 hour Holter monitoring, treadmill exercise testing, signal averaged ECG, and slow kinetic sodium channel blocker loading test (cibenzoline, 1.4 mg/kg).RESULTSAsymptomatic Brugada-type ST shift was found in 12 of 8612 (0.14%) subjects. Eleven of these 12 subjects were followed up. Follow up ECG exhibited persistent Brugada-type ST shift in seven of 11 (63.6%) subjects. ST shift was transformed from a saddle back to a coved type in three subjects. None of the subjects had morphological abnormalities or abnormal tachyarrhythmias. Positive late potentials were found in seven of 11 (63.6%) subjects. Augmentation of ST shift was shown by both submaximal exercise and drug administration in one of the 11 subjects (9.1%).CONCLUSIONSAsymptomatic subjects with Brugada-type ST shift were not unusual, at a rate of 0.14% in the general Japanese population. Almost all of the subjects had some abnormalities in non-invasive secondary examinations. Additional and prospective studies are needed to confirm the clinical significance and the prognosis of asymptomatic Brugada-type ST shift.
Uncomplicated moderate coronary artery dissections after balloon angioplasty: good outcome without stenting
Authors: Albertal M , Van Langenhove G , Regar E , Kay I P , Foley D , Sianos G , Kozuma K , Beijsterveldt T , Carlier S G , Belardi J A , Boersma E , Sousa J E , de Bruyne B , Serruys P W 
Published: July 2021

OBJECTIVETo study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome.METHODS523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection.RESULTSFollowing balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%)v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or ⩾ 2.5 after balloon angioplasty.CONCLUSIONSModerate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome.
Exposure to unhealthy food and beverage advertising during the school commute in Australia
Authors: Trapp Gina , Hooper Paula , Thornton Lukar E , Kennington Kelly , Sartori Ainslie , Wickens Nicole , Billingham Wesley 
Published: July 2021

Background
Food marketing exposure has the potential to influence children’s dietary behaviours and health status, however, few studies have identified how ‘obesogenic’ the outdoor food marketing environment is along public transport (bus and/or train) or walking routes that children take to school.

Methods
Audits of all outdoor advertisements present along likely train, bus and walking routes to 24 secondary schools (ie, 3 routes per school, 72 routes total) were conducted in Perth, Western Australia (WA). The size, content, type and setting of each advertisement were recorded in accordance with the International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support protocol for monitoring outdoor advertising.

Results
Of the 4016 total advertisements observed, almost half were for food (n=1754, 44%) and of these, 80% (n=1397) advertised discretionary (non-core) foods, and 8% (n=138) advertised healthy (core) foods. On average, commuting to school by train, bus and walking exposed Perth schoolchildren to 37.1, 22 and 4.5 discretionary (non-core) food ads per one-way trip to school, respectively.

Conclusions
Children living in Perth, WA experience a high level of exposure to unhealthy outdoor food advertisements during the school commute. Policies which restrict the placement and content of outdoor advertising, could be a useful strategy in the fight against childhood obesity.
Tumor rejection inCblb−/−mice depends on IL-9 and Th9 cells
Authors: Schanz Oliver , Cornez Isabelle , Yajnanarayana Sowmya Parampalli , David Friederike Sophie , Peer Sebastian , Gruber Thomas , Krawitz Peter , Brossart Peter , Heine Annkristin , Landsberg Jenny , Baier Gottfried , Wolf Dominik 
Published: July 2021

BackgroundCasitas B lymphoma-b (Cbl-b) is a central negative regulator of cytotoxic T and natural killer (NK) cells and functions as an intracellular checkpoint in cancer. In particular, Th9 cells support mast cell activation, promote dendritic cell recruitment, enhance the cytolytic function of cytotoxic T lymphocytes and NK cells, and directly kill tumor cells, thereby contributing to tumor immunity. However, the role of Cbl-b in the differentiation and antitumor function of Th9 cells is not sufficiently resolved.MethodsUsingCblb−/−mice, we investigated the effect of knocking outCblbon the differentiation process and function of different T helper cell subsets, focusing on regulatory T cell (Treg) and Th9 cells. We applied single-cell RNA (scRNA) sequencing ofin vitrodifferentiated Th9 cells to understand how Cbl-b shapes the transcriptome and regulates the differentiation and function of Th9 cells. We transferred tumor-model antigen-specificCblb−/−Th9 cells into melanoma-bearing mice and assessed tumor controlin vivo. In addition, we blocked interleukin (IL)-9 in melanoma cell-exposedCblb−/−mice to investigate the role of IL-9 in tumor immunity.ResultsHere, we provide experimental evidence that Cbl-b acts as a rheostat favoring Tregs at the expense of Th9 cell differentiation.Cblb−/−Th9 cells exert superior antitumor activity leading to improved melanoma controlin vivo. Accordingly, blocking IL-9 in melanoma cell-exposedCblb−/−mice reversed their tumor rejection phenotype. Furthermore, scRNA sequencing of in vitro differentiated Th9 cells from naïve T cells isolated from wildtype andCblb−/−animals revealed a transcriptomic basis for increased Th9 cell differentiation.ConclusionWe established IL-9 and Th9 cells as key antitumor executers inCblb−/−animals. This knowledge may be helpful for the future improvement of adoptive T cell therapies in cancer.
Novel germline variant in the histone demethylase and transcription regulator KDM4C induces a multi-cancer phenotype
Authors: Katainen Riku , Donner Iikki , Räisänen Maritta , Berta Davide , Kuosmanen Anna , Kaasinen Eevi , Hietala Marja , Aaltonen Lauri A 
Published: July 2021

BackgroundGenes involved in epigenetic regulation are central for chromatin structure and gene expression. Specific mutations in these might promote carcinogenesis in several tissue types.MethodsWe used exome, whole-genome and Sanger sequencing to detect rare variants shared by seven affected individuals in a striking early-onset multi-cancer family. The only variant that segregated with malignancy resided in a histone demethylase KDM4C. Consequently, we went on to study the epigenetic landscape of the mutation carriers with ATAC, ChIP (chromatin immunoprecipitation) and RNA-sequencing from lymphoblastoid cell lines to identify possible pathogenic effects.ResultsA novel variant in KDM4C, encoding a H3K9me3 histone demethylase and transcription regulator, was found to segregate with malignancy in the family. Based on Roadmap Epigenomics Project data, differentially accessible chromatin regions between the variant carriers and controls enrich to normally H3K9me3-marked chromatin. We could not detect a difference in global H3K9 trimethylation levels. However, carriers of the variant seemed to have more trimethylated H3K9 at transcription start sites. Pathway analyses of ChIP-seq and differential gene expression data suggested that genes regulated through KDM4C interaction partner EZH2 and its interaction partner PLZF are aberrantly expressed in mutation carriers.ConclusionsThe apparent dysregulation of H3K9 trimethylation and KDM4C-associated genes in lymphoblastoid cells supports the hypothesis that the KDM4C variant is causative of the multi-cancer susceptibility in the family. As the variant is ultrarare, located in the conserved catalytic JmjC domain and predicted pathogenic by the majority of available in silico tools, further studies on the role of KDM4C in cancer predisposition are warranted.
#3041 High prevalence of lifetime depressive symptoms in patients referred for clinical amyloid-PET: a retrospective study
Authors: Fitzgerald Anna , Loreto Flavia , Golemme Mara , Win Zarni , Patel Neva , Carswell Christopher , Perry Richard , Malhotra Paresh 
Published: July 2021

Objectives/AimsDepression has been reported as a possible risk factor for Alzheimer’s Disease, but also as one of the clinical features of Alzheimer’s as well as other dementias. Further, depression has long been associated with cognitive impairment in the absence of neurodegeneration (Connors et al. 2018). Here we sought to ascertain the prevalence of clinical depression in patients meeting widely accepted Appropriate Use Criteria for Amyloid PET Imaging (API). We examined the prevalence of lifetime depression in patients undergoing clinical API in a real-world clinical setting and compared our findings with population data from community-dwelling older adults. We also examined whether rates of depression were higher in amyloid positive or negative groups.MethodsOne-hundred-and-eighty-five older adults (mean age 67.079.37, 49% females) underwent diagnostic workup, including API, at the Imperial Memory Clinic between January 2017 and June 2019. API was performed in line with appropriate use criteria after multidisciplinary team discussion. History of depressive symptoms and features of depression were evaluated through a review of hospital records and clinical correspondence. Patients were defined as having a history of depression if there was evidence of previous or current depressive symptoms and/or of a formal diagnosis of depression in their clinical records.ResultsBased on visual reads, 83 individuals had positive Amyloid-PET scans and 102 were negative. Overall, 102 (55%) patients(mean age=66.758.99, 56% females) had a history of lifetime depressive symptoms, compared with just 12 and 19% of elderly individuals in the general population (McDougall et al. 2007; Biddulph et al. 2014). Of the 92 patients for whom further information regarding depression onset were available, 54 (58.7%) had early symptom onset (age <60), and 38 (41.3%) had late symptom onset (age ≥s60). At the time of the clinical assessment at the Imperial Memory Clinic, 71 of those 102 (69.6%) were on active treatment for depression. Finally, depression was not associated with amyloid status (χ2(1) =1.12p=.26), with 42 (41.2%) amyloid-positive and 60 (58.8%) amyloid-negative patients reporting a history of depression.ConclusionsOver half of patients with suspected cognitive impairment and meeting appropriate use criteria for clinical API had a history of depression, regardless of amyloid status. Depression is an important but incompletely understood factor in referral for evaluation with Amyloid-PET.