Recent Changes in Storm Track over the Southeast Europe: A Mechanism for Changes in Extreme Cyclone Variability

Recent changes in cyclone tracks crossing Southeast Europe are investigated for the last few decades (1980–1999 compared with 2000–2019) using a developed objective method. The response in number, severity, and persistence of the tracks are analyzed based on the source of origin (the Mediterranean Sea sub-domains) and the target area (Romania-centered domain). In winter, extreme cyclones became more frequent in the south and were also more persistent in the northeast of Romania. In summer, these became more intense and frequent, mainly over the south and southeast of Romania, where they also showed a significant increase in persistence. The regional extreme changes are related to polar jet displacements and further enhanced by the coupling of the sub-tropical jet in the Euro-Atlantic area, such as southwestwards shift in winter jets and a split-type configuration that shifts northeastwards and southeastwards in the summer. These provide a mechanism for regional variability of extreme cyclones through two paths, respectively, by shifting the origins of the tracks and by shifting the interaction between the anomaly jet streaks and the climatological storm tracks. Large-scale drivers of these changes are analyzed in relation to the main modes of atmospheric variability. The tracks number over the target domain is mainly driven during the cold season through a combined action of AO and Polar–European modes, and in summer by the AMO and East-Asian modes. These links and the circulation mode’s recent variability are consistent with changes found in the jet and storm tracks

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC

State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC