No abstract

Purpose. Over recent decades, no consensus has yet been reached on the optimal approach to cosmetic evaluation following breast-conserving therapy (BCT). The present study compared the strengths and weaknesses of the BCCT.core software with a 10-member panel from various backgrounds. Methods. Digital photographs of 109 consecutive patients after BCT were evaluated for 7 items by a panel consisting of 2 breast surgeons, 2 residents, 2 laypersons, and 4 plastic surgeons. All photographs were objectively evaluated using the BCCT.core software (version 20), and an overall cosmetic outcome score was reached using a four-point Likert scale. Results. Based on the mean BCCT.core software score, 41% of all patients had fair or poor overall cosmetic results (10% poor), compared with 51% (14% poor) obtained with panel evaluation. Mean overall BCCT.core score and mean overall panel score substantially agreed (weighted kappa: 0.68). By contrast, analysis of the evaluation of scar tissue revealed large discrepancies between the BCCT.core software and the panel. The analysis of subgroups formed from different combinations of the panel members still showed substantial agreement with the BCCT.core software (range 0.64–0.69), independent of personal background. Conclusions. Although the analysis of scar tissue by the software shows room for improvement, the BCCT.core represents a valid and efficient alternative to panel evaluation.

The current study suggests that the favorable prognosis for patients with HPV-positive HNSCC does not seem to be related to an intrinsic sensitivity of these tumor cells to chemotherapy or radiation in vitro.

Generation of neuronal cultures from induced pluripotent stem cells (hiPSCs) serve the studies of human brain disorders. However we lack neuronal networks with balanced excitatory-inhibitory activities, which are suitable for single cell analysis. We generated low-density networks of hPSC-derived GABAergic and glutamatergic cortical neurons. We used two different co-culture models with astrocytes. We show that these cultures have balanced excitatory-inhibitory synaptic identities using confocal microscopy, electrophysiological recordings, calcium imaging and mRNA analysis. These simple and robust protocols offer the opportunity for single-cell to multi-level analysis of patient hiPSC-derived cortical excitatory-inhibitory networks; thereby creating advanced tools to study disease mechanisms underlying neurodevelopmental disorders.

Objective: Astrocytes have gained attention as important players in neurological disease. In line with their heterogeneous character, defects in specific astrocyte subtypes have been identified. Leukodystrophy vanishing white matter (VWM) shows selective vulnerability in white matter astrocytes, but the underlying mechanisms remain unclear. Induced pluripotent stem cell technology is being extensively explored in studies of pathophysiology and regenerative medicine. However, models for distinct astrocyte subtypes for VWM are lacking, thereby hampering identification of disease-specific pathways. Methods: Here, we characterize human and mouse pluripotent stem cell-derived gray and white matter astrocyte subtypes to generate an in vitro VWM model. We examined morphology and functionality, and used coculture methods, high-content microscopy, and RNA sequencing to study VWM cultures. Results: We found intrinsic vulnerability in specific astrocyte subpopulations in VWM. When comparing VWM and control cultures, white matter-like astrocytes inhibited oligodendrocyte maturation, and showed affected pathways in both human and mouse cultures, involving the immune system and extracellular matrix. Interestingly, human white matter-like astrocytes presented additional, human-specific disease mechanisms, such as neuronal and mitochondrial functioning. Interpretation: Astrocyte subtype cultures revealed disease-specific pathways in VWM. Cross-validation of human-and mouse-derived protocols identified human-specific disease aspects. This study provides new insights into VWM disease mechanisms, which helps the development of in vivo regenerative applications, and we further present strategies to study astrocyte subtype vulnerability in neurological disease.