Deciphering the landscape of transcriptional heterogeneity across cancer.

By integrating scRNA-seq datasets across 77 studies and 24 cancer types, in Nature, Gavish et al. uncover recurrent patterns of gene expression that explain a significant proportion of transcriptomic heterogeneity observed in cancer and explore their functional significance.

Genomic-transcriptomic evolution in lung cancer and metastasis.

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy1. 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 study2,3. 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.

The accuracy of magnetic resonance imaging in the assessment of glenohumeral articular degenerative disease.

Degenerative joint disease is a major source of disability in the world with over 43 million individuals suffering from the affliction in the United States alone. It is the most common cause of activity limitation in individuals over 65 years of age. While much of the focus in recent years has been on osteoarthritis of the hips and knees, shoulder degenerative disease is becoming a more commonly recognized source of morbidity with a wide range of associated lifestyle-limiting disabilities. At the same time therapeutic options for treatment of degenerative joint disease are rapidly increasing, both medically and surgically. This combination of factors makes it necessary to determine a reliable, noninvasive means by which to accurately diagnose the early changes of shoulder degenerative disease. The clinical diagnosis of shoulder osteoarthritis is extremely challenging. There are numerous existing mimickers such as rotator cuff injuries, bursitis, and impingement syndrome. While the conventional radiographic findings are well recognized, they are generally late developments in the course of the disease when therapeutic options are more limited and less effective. Additionally, plain film evaluation has poor sensitivity for the detection of many of the alternative diagnoses that may underlie chronic shoulder pain. Though correlative findings are seen in MR imaging, its role in evaluating glenohumeral degenerative changes has been limited, with much of the focus being on the identification of tendinous and ligamentous disease or osseous tumors. A retrospective analysis is presented which demonstrates the efficacy of MR imaging in assessing GHJ OA, as well as shows that dedicated evaluation for specific degenerative findings results in improved detection rates of GHJ degenerative disease. It is believed that with improved detection and reporting, improved clinical care for this prevalent disorder may be achieved.

A convenient method for the computer-aided molecular design of carborane containing compounds.

Computer-aided molecular design (CAMD) of carborane containing compounds is of growing interest for scientists involved in boron neutron capture therapy (BNCT) and other pharmaceutical applications. However, the complex organo-metallic structures of carboranes pose difficulties in modeling and docking of these structures. This is the first report of a new strategy for modeling and docking of carborane containing molecules with the readily available software packages HyperChem, SYBYL and FlexX. It is intended as a guide for boron chemists interested in using CAMD of carborane containing agents for medical applications such as BNCT.

Your diagnosis? Posterior shoulder dislocation.

Accurate diagnosis of posterior shoulder dislocation requires a high index of suspicion in shoulder trauma patients and proper radiographic evaluation. This case highlights the importance of obtaining axillary views in shoulder trauma cases.

The influence of water vapour on the determination of glutaraldehyde vapour concentrations using an electrochemical fuel cell sensor.

The effects of relative humidity (40-90% RH) and varying glutaraldehyde vapour concentrations (< 0.1 ppm) on the response of an electrochemical fuel cell sensor have been investigated over time (0-400 s). These studies have identified changes in the response of the fuel cell with time after sampling. In particular, it has been found that the maximum cell output for water vapour occurs ca. 10 s after sampling whilst the response to glutaraldehyde occurs much later (> 100 s). For mixtures containing different ratios of water and glutaraldehyde vapours, the time taken to reach maximum fuel cell response varies between 10 and 100 s, depending on the ratio of the two vapours. For instance, glutaraldehyde vapour containing higher % RH has been found to result in shorter times to reach maximum fuel cell response. A comparison was made between measuring glutaraldehyde vapour concentrations in the presence of water vapour at the maximum fuel cell response and also at a fixed interval (240 s) after sampling. Such a comparison resulted in a reduction in the standard error from 36% to 5% for a glutaraldehyde vapour sample (0.023 ppm) measured at different values of relative humidity (40 to 80%). Examination of the effect of the sample volume (30-60 ml) on the response of the fuel cell shows, as expected, an approximate doubling of the fuel cell response. Optimisation of the fuel cell measurement parameters to measure a 60 ml sample leads to a lowering of the limit of detection from 0.083 ppm (for data taken at the maximum cell response) to 0.017 ppm for data measured 240 s after sampling. In the light of recent reductions in the legal limits for exposure to glutaraldehyde, this has important implications for the measurement of glutaraldehyde vapour in the workplace.

Association of biceps tendon tears with rotator cuff abnormalities: degree of correlation with tears of the anterior and superior portions of the rotator cuff.

OBJECTIVE: This study was performed to examine the relationship and association of abnormalities seen in the long head of the biceps brachii tendon to abnormal findings in the rotator cuff. MATERIALS AND METHODS: One hundred eleven patients underwent MR imaging for shoulder pain followed by arthroscopic or open shoulder surgery from January 1997 to December 2000. Patients were identified by a retrospective search, and all consecutive patients having undergone both MR imaging and surgery were included in the patient cohort. Official MR imaging interpretations were compared with operative reports, and all findings were recorded. RESULTS: Twenty-three patients were identified with partial- or full-thickness tears of the long head of the biceps tendon. The sensitivity, specificity, and accuracy of unenhanced MR imaging of the shoulder for detecting these bicipital tears were 52%, 86%, and 79%, respectively. When a tear was present in the biceps tendon, the prevalence of supraspinatous, infraspinatus, and subscapularis tendon tears was 96.2%, 34.6%, and 47.1%, respectively. Patients with biceps tendon tears were significantly more likely to also have subscapularis tendon tears (p < 0.0001) and supraspinatous tendon tears (p < 0.008) than those patients who did not have biceps tendon tears. No significant relationship was found between the presence or absence of a biceps tendon tear and the presence or absence of a infraspinatus or teres minor tendon tear (p = 0.17). CONCLUSION: Tears of the long head of the biceps tendon have a statistically significant association with tears of the anterior and superior rotator cuff and are highly correlated with tears of the supraspinatous and subscapularis tendons. When tears of these tendons are detected, specific attention directed toward the long biceps tendon is warranted to characterize the status of this structure that provides additional stability to the shoulder joint.