GCTB is an osteolytic, locally-aggressive, rarely-metastasizing tumour, characterized by abundance of osteoclastlike giant cells, induced by neoplastic mononuclear cells expressing high-levels of... Show moreGCTB is an osteolytic, locally-aggressive, rarely-metastasizing tumour, characterized by abundance of osteoclastlike giant cells, induced by neoplastic mononuclear cells expressing high-levels of the receptor activator of nuclear factor Kappa-B ligand (RANKL), a mediator of osteoclast activation. Although the mainstay of treatment is complete tumour removal with preservation of bone, therapy with denosumab, an inhibitor of RANKL, has been introduced for selected cases. Objectives: Denosumab-treated GCTB (DT-GCTB) was reported to show a wide spectrum of histological changes such as depletion of osteoclast-like giant cells and intralesional bone deposition, which may lead to diagnostic difficulties. We investigated clinicopathologic and molecular features of DT-GCTB, matched with pre-therapy samples. Participants: 21 cases were included (13 females, 8 males), aged 15 to 64 (median, 30 years). Results: DT-GCTB showed development of sclerotic neocortex and varying degrees of osteosclerosis radiographically. Marked depletion of giant cells, different degree of ossification, fibrosis, and proliferation of mononuclear cells was observed. Staining for H3.3G34W was positive in mononuclear cells in 19 cases (90.5%), while one negative case was positive for H3.3G34V. H3F3A G34W mutation was confirmed in 17 of 19 cases (89.5%), corresponding to nuclear staining with H3.3 G34W antibody. G34L mutation was detected in one G34W negative case, in which H3.3 G34V nuclear positive staining was observed, possibly due to cross-reaction. Conclusions: Post-therapy tumours still exhibit a similar mutation profile, while significantly differing from classic GCTB morphologically. Correlation with history of denosumab administration, awareness of features of DT-GCTB, IHC and molecular studies for histone H3 mutations are important in its assessment. Show less
Variational quantum eigensolvers offer a small-scale testbed to demonstrate the performance of error mitigation techniques with low experimental overhead. We present successful error mitigation by... Show moreVariational quantum eigensolvers offer a small-scale testbed to demonstrate the performance of error mitigation techniques with low experimental overhead. We present successful error mitigation by applying the recently proposed symmetry verification technique to the experimental estimation of the ground-state energy and ground state of the hydrogen molecule. A finely adjustable exchange interaction between two qubits in a circuit QED processor efficiently prepares variational ansatz states in the single-excitation subspace respecting the parity symmetry of the qubit-mapped Hamiltonian. Symmetry verification improves the energy and state estimates by mitigating the effects of qubit relaxation and residual qubit excitation, which violate the symmetry. A full-density-matrix simulation matching the experiment dissects the contribution of these mechanisms from other calibrated error sources. Enforcing positivity of the measured density matrix via scalable convex optimization correlates the energy and state estimate improvements when using symmetry verification, with interesting implications for determining system properties beyond the ground-state energy. Show less
