Pseudocell Tracer-A method for inferring dynamic trajectories using scRNAseq and its application to B cells undergoing immunoglobulin class switch recombination.

Single cell RNA sequencing (scRNAseq) can be used to infer a temporal ordering of cellular states. Current methods for the inference of cellular trajectories rely on unbiased dimensionality reduction techniques. However, such biologically agnostic ordering can prove difficult for modeling complex developmental or differentiation processes. The cellular heterogeneity of dynamic biological compartments can result in sparse sampling of key intermediate cell states. To overcome these limitations, we develop a supervised machine learning framework, called Pseudocell Tracer, which infers trajectories in pseudospace rather than in pseudotime. The method uses a supervised encoder, trained with adjacent biological information, to project scRNAseq data into a low-dimensional manifold that maps the transcriptional states a cell can occupy. Then a generative adversarial network (GAN) is used to simulate pesudocells at regular intervals along a virtual cell-state axis. We demonstrate the utility of Pseudocell Tracer by modeling B cells undergoing immunoglobulin class switch recombination (CSR) during a prototypic antigen-induced antibody response. Our results revealed an ordering of key transcription factors regulating CSR to the IgG1 isotype, including the concomitant expression of Nfkb1 and Stat6 prior to the upregulation of Bach2 expression. Furthermore, the expression dynamics of genes encoding cytokine receptors suggest a poised IL-4 signaling state that preceeds CSR to the IgG1 isotype.

Tendon Disorders.

The clinically important tendons around the elbow include the biceps and triceps brachii and the flexor and extensor muscles of the forearm. Familiarity with the normal magnetic resonance (MR) appearance of these structures facilitates the MR diagnosis of tendon abnormalities. Often referred to as epicondylitis, degeneration of the flexor or extensor groups is a common clinical complaint, treated conservatively and usually not requiring MR imaging. Imaging may play a role in unusual or severe cases; elevated signal in the appropriate common tendon origin is typically seen on T2 weighted images. Significant injury or disruption of the distal biceps or triceps tendons is a rare event, usually related to an acute event. Discontinuity of these tendons is best imaged using sagittal and axial T2 weighted sequences. Partial tears may demonstrate tendon irregularity and elevated signal within and around the tendon.

Intra-articular ganglion arising from the meniscofemoral ligament of Humphrey.

We present a case of an intra-articular ganglion of the knee arising from the anterior meniscofemoral ligament of Humphrey. The MR imaging and arthroscopic appearance of the lesion are illustrated.

Grading articular cartilage of the knee using fast spin-echo proton density-weighted MR imaging without fat suppression.

OBJECTIVE: The objective of this work was to determine the accuracy of fast spin-echo proton density-weighted MR imaging in the evaluation of the articular cartilage of the knee using arthroscopy as a gold standard. MATERIALS AND METHODS: We retrospectively reviewed MR images of the knee in 54 patients for whom arthroscopic results were available. All MR imaging studies included fast spin-echo proton density-weighted coronal and axial sequences as part of our routine protocol. Evaluation of the articular surfaces was performed by three independent observers who were unaware of the arthroscopic results. The cartilage surfaces were graded using a 3-point system, and results were compared with arthroscopic findings. RESULTS: Of 324 cartilage surfaces evaluated, arthroscopy showed 241 surfaces as normal, 56 as containing partial-thickness defects, and 27 as containing full-thickness defects. Compared with arthroscopic data, sensitivity of MR imaging for the three reviewers was 59-73.5%; specificity, 86.7-90.5%; positive predictive value, 60.5-72.6%; negative predictive value, 86.0-90.8%; and accuracy, 79.6-86.1%. Interobserver variability for the presence of disease, which was measured using the kappa statistic, was 0.63. CONCLUSION: Fast spin-echo proton density-weighted MR imaging sequences can be used to evaluate the cartilage of the knee with accuracy comparable to that of previously reported cartilage-specific sequences.