Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients

The True Dislocation Incidence following Elective Total Hip Replacement in Sweden : How Does It Relate to the Revision Rate?

(1) Background: The true dislocation incidence following THA is difficult to ascertain in population-based cohorts. In this study, we explored the cumulative dislocation incidence (CDI), the relationship between the incidence of dislocation and revision surgery, patient- and surgery-related factors in patients dislocating once or multiple times, and differences between patients being revised for dislocation or not. (2) Methods: We designed an observational longitudinal cohort study linking registers. All patients with a full dataset who underwent an elective unilateral THA between 1999 and 2014 were included. The CDI and the time from the index THA to the first dislocation or to revision were estimated using the Kaplan-Meier (KM) method, giving cumulative dislocation and revision incidences at different time points. (3) Results: 136,810 patients undergoing elective unilateral THA were available for the analysis. The 30-day CDI was estimated at 0.9% (0.9-1.0). The revision rate for dislocation throughout the study period remained much lower. A total of 51.2% (CI 49.6-52.8) suffered a further dislocation within 1 year. Only 10.9% of the patients with a dislocation within the first year postoperatively underwent a revision for dislocation. (4) Discussion: The CDI after elective THA was expectedly considerably higher than the revision incidence. Further studies investigating differences between single and multiple dislocators and the criteria by which patients are offered revision surgery following dislocation are urgently needed

Pulsed electromagnetic fields increase osteogenetic commitment of MSCs via the mTOR pathway in TNF-\u3b1 mediated inflammatory conditions: An in-vitro study

Pulsed electromagnetic fields (PEMFs) have been considered a potential treatment modality for fracture healing, however, the mechanism of their action remains unclear. Mammalian target of rapamycin (mTOR) signaling may affect osteoblast proliferation and differentiation. This study aimed to assess the osteogenic differentiation of mesenchymal stem cells (MSCs) under PEMF stimulation and the potential involvement of mTOR signaling pathway in this process. PEMFs were generated by a novel miniaturized electromagnetic device. Potential changes in the expression of mTOR pathway components, including receptors, ligands and nuclear target genes, and their correlation with osteogenic markers and transcription factors were analyzed. Involvement of the mTOR pathway in osteogenesis was also studied in the presence of proinflammatory mediators. PEMF exposure increased cell proliferation and adhesion and the osteogenic commitment of MSCs even in inflammatory conditions. Osteogenic-related genes were over-expressed following PEMF treatment. Our results confirm that PEMFs contribute to activation of the mTOR pathway via upregulation of the proteins AKT, MAPP kinase, and RRAGA, suggesting that activation of the mTOR pathway is required for PEMF-stimulated osteogenic differentiation. Our findings provide insights into how PEMFs influence osteogenic differentiation in normal and inflammatory environments

AOI and AOF example.

<p>A heat map. The AOFs are represented by the blue lines encircling the red areas of the heat map. The AOIs are represented by the orange circles reflecting the pathological areas evidencing FAI syndrome.</p

An heatmap example of an expert vs. a resident.

<p>this figure represents a comparison between two heat maps (those of the experts and the residents).This figure contains 3 pathologic areas, the hip joints and suspected Spina Bifida. This comparison emphasizes the differences in experts’ and residents’ attention to AOFs and their relation to AOIs.</p

A comparison and RQA areas example.

<p>A radiograph with a comparison marked by a yellow line. This comparison represents a saccadic movement between two fixations in opposite symmetric areas. The radiograph also represent eight highlighted FOI areas where the unmarked area is considered as the ninth area. These areas were used for the RQA.</p

Time series and recurrence plot by expertise.

<p>Fig 2 a and b present representative time series of an expert and a novice and Fig 2c and d present the corresponding recurrence plots.</p