Bilateral superficial ulnar artery with high origin from the axillary artery: its anatomy and clinical significance

The superficial ulnar artery (SUA) is a rare anatomical variant that usually arises either in the axilla or the arm and runs a superficial course in the forearm, enters the hand, and participates in the formation of superficial palmar arch. During the routine dissection of cadavers in the department of anatomy, whilst preparing the specimen for medical students, an unusual bilateral branch of the axillary artery was found in one of the cadavers: a rare variant of the artery known as SUA, which originates from the 2nd part of the axillary arteries of both sides. The SUA is a known anatomical variant, but the bilateral high origin from the 2nd part of the axillary artery is extremely unusual. Its occurrence is of great clinical importance to the surgical and radiological departments

Proposed classification for interproximal contacts of primary molars using CBCT: a pilot study [version 2; referees: 2 approved]

Background: Interproximal contact areas in primary teeth are known to be broader, flatter, and situated more gingivally than in permanent teeth. The objective of the present study was to evaluate the different types of intact interproximal contact areas in primary teeth using cone beam computed tomography (CBCT) among children. Methods: A cross-sectional study was designed with 74 contacts from 28 existing CBCT images of children aged between 3 and 14 years, obtained from the Indian Dental Education Academy, Chennai, India. The shape of the contact area was observed at three levels, the coronal, middle, and apical thirds, in three different sections of CBCT. Prevalence of the types of contact areas was expressed in the form of numbers and percentages. Results: The weighted Cohen’s kappa values for inter-examiner reliability was 0.893 at baseline. Results exhibited four different types of contact areas between the primary molars, namely, O type, X type, I type, and S type, based on the shapes observed; hence, the proposed classification is referred to as OXIS. The most common pattern seen was I (66.2%), followed by X (21.6%), O (9.4%) and the least common was S (2.7%). Conclusion: The three-dimensional evaluation of intact interproximal contact areas between primary molars are of four types, O,X, I and S

Proposed classification for interproximal contacts of primary molars using CBCT: a pilot study [version 1; referees: 2 approved]

Background: Contact areas in primary teeth are known to be broader, flatter, and situated more gingivally than in permanent teeth. The objective of the present study was to evaluate the different types of intact contact areas in primary teeth using cone beam computed tomography (CBCT) among children. Methods: A cross-sectional study was designed with 74 contacts from 28 existing CBCT images of patients aged between 3 and 14 years, obtained from the Indian Dental Education Academy, Chennai, India. The shape of the contact area was observed at three levels, the coronal, middle, and apical thirds, in three different sections of CBCT. The weighted Cohen’s kappa values for inter-examiner reliability was 0.893 at baseline. Prevalence of the types of contact areas was expressed in the form of numbers and percentages. Results: Results exhibited four different types of contact areas between the primary molars, namely, O type, X type, I type, and S type, based on the shapes observed; hence, the proposed classification is referred to as OXIS. The most common pattern seen was I (66.2%), followed by X (21.6%), O (9.4%) and the least common was S (2.7%). Conclusion: The three-dimensional evaluation of intact interproximal contact areas between primary molars are of four types

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. 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 deaths. 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

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis