129 research outputs found
Stereocomplex formation in ABA triblock copolymers of poly(lactide) (A) and poly(ethylene glycol) (B)
Two series of triblock copolymers of poly(ethylene glycol) (PEG, number-average molecular weight [bar M ]n = 6000) and poly(L-lactide) (PLLA) or poly(D-lactide) (PDLA) were prepared by ring-opening polymerization of lactide initiated by PEG end groups using stannous octoate as a catalyst, either in refluxing toluene or in the melt at 175°C. The weight percentage of PLA in the polymers varied between 15 and 75 wt.-%. Blends of polymers containing blocks of opposite chirality were prepared by co-precipitation from homogeneous solutions. The melting temperatures of the crystalline PEG and PLA phases strongly depended on the composition of the polymers. The melting temperature of the PLA phase in the blends was approximately 40°C higher than that of the single block copolymers. Stereocomplex formation between blocks of enantiomeric poly(lactides) in PEG/PLA block copolymers was established for the first time. Water uptake of polymeric films prepared by solution casting was solely determined by the PEG content of the film
Polymerization of ethylene oxide using yttrium isopropoxide
Well defined poly(ethylene oxide)s were prepared using yttrium isopropoxide as an initiator. End group analysis using 1H- and 13C NMR spectroscopy revealed that only polymers with isopropyl ether and hydroxyl end groups were produced. The molecular weight is controlled by the initial amount of initiator added and low polydispersity polymer (Mw/Mn ≈ 1.1) was isolated. Sequential polymerization indicated the suitability of this initiator for macromolecular engineering
Stereocomplex formation in AB di-block copolymers of poly(ε-caprolactone) (A) and poly(lactide) (B)
The thermal properties of two series of AB di-block copolymers of poly(ε-caprolactone) (A) and poly(lactide) (B) and their blends were studied. Each series contained poly(lactide) blocks of opposite chirality. The length of the poly(ε-caprolactone) blocks was not varied (DP = 70), whereas the poly(lactide) blocks were of varying length (DP = 5 - 80). Blends of polymers containing blocks of opposite chirality were prepared by mixing in solution. The melting temperature of the PLA phase was raised by approximately 55 °C in the blends due to stereocomplex formation. The melting temperatures of the crystalline PCL and PLA phases strongly depended on the composition of the block copolymers
Anti-C1q autoantibodies may not serve as an adequate biomarker for lung manifestations in systemic sclerosis: a single-centre, cross-sectional study
Pathophysiology and treatment of rheumatic disease
Mechanical performance and healing patterns of the novel sirolimus-eluting bioresorbable Fantom scaffold: 6-month and 9-month follow-up by optical coherence tomography in the FANTOM II study
Objectives We aimed to evaluate the mechanical properties
and healing patterns 6 and 9 months after implantation of the
sirolimus-eluting Fantom bioresorbable scaffold (BRS).
Background The Fantom BRS (Reva Medical, San Diego,
USA) has differentiating properties including radiopacity,
strut thickness of 125 µm, high expansion capacity and
has demonstrated favourable mid-term clinical and
angiographic outcomes.
Methods and results FANTOM II was a prospective,
single arm study with implantation of the Fantom BRS
in 240 patients with stable angina pectoris. Guidance by
optical coherence tomography (OCT) was encouraged and
was repeated at 6-month (cohort A) or 9-month follow-up
(cohort B). Matched baseline and follow-up OCT recordings
were available in 152 patients. In-scaffold mean lumen
area in cohort A was 6.8±1.7mm2
and 5.7±1.4mm2
at baseline and follow-up (p<0.0001) and was
7.2±1.6mm2
and 5.6±1.4mm2
in cohort B (p<0.0001).
Mean scaffold area remained stable from 7.1±1.5mm2
at baseline to 7.2±1.4mm2
at 6 months (p=0.12), and
from 7.4±1.5mm2
to 7.3±1.4mm2
at 9 months. Strut
malapposition was median 0.8 (IQR 0.0;3.5)% and 1.8 (IQR
0.3;6.0)% at baseline and was 0.0 (IQR 0.0;0.0)% in both
groups at 6-month and 9-month follow-up. Strut tissue
coverage was 98.1 (IQR 95.9;99.4)% at 6 months and
98.9 (IQR 98.3;100.0)% at 9 months.
Conclusions The novel Fantom BRS had favourable
healing patterns at 6-month and 9-month follow-up as
malapposition was effectively resolved and strut coverage
was almost complete. The scaffold remained stable
through follow-up with no signs of systematic late recoil
The artificial intelligence-based model ANORAK improves histopathological grading of lung adenocarcinoma
The introduction of the International Association for the Study of Lung Cancer grading system has furthered interest in histopathological grading for risk stratification in lung adenocarcinoma. Complex morphology and high intratumoral heterogeneity present challenges to pathologists, prompting the development of artificial intelligence (AI) methods. Here we developed ANORAK (pyrAmid pooliNg crOss stReam Attention networK), encoding multiresolution inputs with an attention mechanism, to delineate growth patterns from hematoxylin and eosin-stained slides. In 1,372 lung adenocarcinomas across four independent cohorts, AI-based grading was prognostic of disease-free survival, and further assisted pathologists by consistently improving prognostication in stage I tumors. Tumors with discrepant patterns between AI and pathologists had notably higher intratumoral heterogeneity. Furthermore, ANORAK facilitates the morphological and spatial assessment of the acinar pattern, capturing acinus variations with pattern transition. Collectively, our AI method enabled the precision quantification and morphology investigation of growth patterns, reflecting intratumoral histological transitions in lung adenocarcinoma
Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and ‘tumor spread through air spaces’ were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk
The evolution of lung cancer and impact of subclonal selection in TRACERx
Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource
The evolution of non-small cell lung cancer metastases in TRACERx
Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse
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