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Neuroendocrine tumors (NETs) are highly vascular neoplasms overexpressing vascular endothelial growth factor (VEGF) as well as VEGF receptors (VEGFR). Axitinib is a potent, selective inhibitor of VEGFR-1, -2 and -3, currently approved for the treatment of advanced renal cell carcinoma. We performed an open-label, two-stage design, phase II trial of axitinib 5mg twice daily in patients with progressive unresectable/metastatic low-to-intermediate grade carcinoid tumors. The primary end points were progression-free survival (PFS) and 12-month PFS rate. The secondary end points included time to treatment failure (TTF), overall survival (OS), overall radiographic response rate (ORR), biochemical response rate and safety. A total of 30 patients were enrolled and assessable for toxicity; 22 patients were assessable for response. After a median follow-up of 29months, we observed a median PFS of 26.7months (95% CI, 11.4-35.1), with a 12-month PFS rate of 74.5% (±10.2). The median OS was 45.3 months (95% CI, 24.4-45.3), and the median TTF was 9.6months (95% CI, 5.5-12). The best radiographic response was partial response (PR) in 1/30 (3%) and stable disease (SD) in 21/30 patients (70%); 8/30 patients (27%) were unevaluable due to early withdrawal due to toxicity. Hypertension was the most common toxicity that developed in 27 patients (90%). Grade 3/4 hypertension was recorded in 19 patients (63%), leading to treatment discontinuation in six patients (20%). Although axitinib appears to have an inhibitory effect on tumor growth in patients with advanced, progressive carcinoid tumors, the high rate of grade 3/4 hypertension may represent a potential impediment to its use in unselected patients.

Open‐vent volcanoes continuously emit magmatic products and frequently feature multiple adjacent craters. Temporal shifts of thermal emissions between craters are especially detectable by InfraRed satellites. Here, SENTINEL‐2 and LANDSAT‐8/9 Short Wave InfraRed (SWIR) high‐spatial resolution satellite data, are combined to investigate 10 years (2013–2023) of thermal activity at Stromboli volcano (Italy). The correlation between Volcanic Radiative Power (VRP, in Watts) and Volcanic Radiative Energy (VRE, in Joules), retrieved by moderate MODIS and VIIRS Middle InfraRed (MIR) data, with the Thermal Index SWIR (TISWIR) data, allows us to quantify long‐term series of heat fluxes (VRPSWIR) and energy (VRESWIR). Combining moderate and higher spatial resolution data and fitting cumulative trends of TISWIR with VREMIR allows to measure thermal activity sourced by single craters during Strombolian activity. Long‐term results highlight that thermal emissions are clustered in the northern and southern parts of the crater terrace, with total energy emitted (∼12 × 1014 J) equally distributed. The thermal increase since April 2017 marked a reactivation of shallow magma transportation and an intensification of the activity after the 2014 eruption. Distinct thermal behaviors are shown by the NE, C, and SW craters, related to mechanisms of explosions. We found that short‐term thermal variations match well those resolved by ground‐based signals, and the NE crater as the most sensitive to the transition to higher‐intensity activity. Our multispatial/multisensory investigation allows, for the first time, the long‐term quantification of heat flux from Stromboli's craters, with an improved understanding of open‐vent dynamics and a new approach to monitor multiple active craters. Plain Language Summary: Stromboli is a volcano in southern Italy, historically well‐known, considered unique and fascinating for its persistent emission of magma and gas through multiple adjacent craters lasting for millennia. This study focuses on tracking the thermal activity of Stromboli using modern satellite data over 2013–2023, with unprecedented levels of detail able to distinguish the heat released by single craters. The analysis revealed that most thermal emissions at Stromboli were concentrated in two primary sectors of the summit terrace. Notably, a significant increase in thermal activity was observed since April 2017, indicating a resurgence in volcanic activity after a period of relatively calm following the previous eruption. Distinct thermal behaviors of the three historically active craters of Stromboli have been recognized and reconciled with different styles of volcanic explosions. Furthermore, the study identified patterns of heat release within Stromboli's main craters which agreed with the fluctuations in gas emissions and explosive activity characterizing the volcano. Overall, this comprehensive analysis provides valuable insights to scientists and volcano‐involved communities into the long‐term quantification of heat flux from multiple craters at Stromboli, contributing to a better understanding of open‐vent eruptive dynamics and enhancing continuous monitoring of Stromboli and similar volcanoes. Key Points: Ten years (2013–2023) quantification of heat flux VRPSWIR from active craters at Stromboli using Sentinel‐2 and Landsat‐8/‐9 SWIR imagesTwo main thermal clusters emitting ∼12 × 1014 J. Thermal increase since April 2017 marks a reactivation of intense Strombolian activityNE, C, and SW craters show distinct thermal behavior, with the NE as the most energetic. VRPSWIR tracks transition to more explosive phases [ABSTRACT FROM AUTHOR]

Rania Shamekh,1 Mauro Cives,2 Jaime Mejia,3 Domenico Coppola,4 1Department of Pathology, University of South Florida, 2Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA; 3Department of Pathology, Institutode Patologia Mejia Jimenez, Cali, Colombia; 4Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL, USA Abstract: Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of death worldwide. It accounts for >9% of all cancers. One of the pathogenic factors of CRC is germline mutation, leading to alteration and inactivation in the mismatch repair (MMR) genes. The aim of the study is to compare the frequency of alterations in MMR protein expression in Caucasian CRC patients with Colombian CRC patients. A total of 45 Colombians and 48 Caucasians with CRC were studied. The microsatellite instability status of tumors was determined in primary CRC by immunohistochemistry using the automated Ventana Ultra. The combined loss of MLH1 and PMS2 was the most common alteration in both Colombian (11%, five out of 45) and Caucasian (12%, six out of 48) CRC patients. Interestingly, the loss of PMS2 expression in the presence of intact MLH1 was the second most common alteration in Colombians (8%, four out of 45), which was never seen in the Caucasian cohort (P=0.05). The loss of MLH1 alone and the combined loss of MSH6 and PMS2 expression were only observed in one out of 45 (2%) Colombians but not in Caucasians. The combined loss of MSH2 and MSH6 was not observed in any of the patients studied. The preliminary findings support a significant difference in alterations of MMR protein expression in Colombian CRC patients compared with Caucasian CRC patients. These findings are novel and warrant further studies in larger cohorts. Keywords: colon cancer, MSI, MMR, immunohistochemistry

Bagana is a remote, highly active volcano, located on Bougainville Island in southeastern Papua New Guinea. The volcano has exhibited sustained and prodigious sulfur dioxide gas emissions in recent decades, accompanied by frequent episodes of lava extrusion. The remote location of Bagana and its persistent activity have made it a valuable case study for satellite observations of active volcanism. This remoteness has also left many features of Bagana relatively unexplored. Here, we present the first measurements of volcanic gas composition, achieved by unoccupied aerial system (UAS) flights through the volcano's summit plume, and a payload comprising a miniaturized MultiGAS. We combine our measurements of the molar CO2/SO2 ratio in the plume with coincident remote sensing measurements (ground‐ and satellite‐based) of SO2 emission rate to compute the first estimate of CO2 flux at Bagana. We report low SO2 and CO2 fluxes at Bagana from our fieldwork in September 2019, ∼320 ± 76 td−1 and ∼320 ± 84 td−1, respectively, which we attribute to the volcano's low level of activity at the time of our visit. We use satellite observations to demonstrate that Bagana's activity and emissions behavior are highly variable and advance the argument that such variability is likely an inherent feature of many volcanoes worldwide and yet is inadequately captured by our extant volcanic gas inventories, which are often biased to sporadic measurements. We argue that there is great value in the use of UAS combined with MultiGAS‐type instruments for remote monitoring of gas emissions from other inaccessible volcanoes. Plain Language Summary: Bagana is a remote and highly active volcano in southeastern Papua New Guinea (PNG). Historically, it has been among the most active volcanoes in PNG, notable for its long‐lived eruptions and sustained gas emissions. Bagana has only been infrequently studied before now. We use unoccupied aerial systems (drones) along with ground‐ and satellite‐based remote sensing data to characterize the chemical composition and flux of Bagana's gas emissions and place these in the context of global volcanic emissions. Owing to low activity during the time of our fieldwork, we report lower than anticipated emissions of carbon dioxide and sulfur dioxide from Bagana. We argue that characterizing highly variable volcanic emissions is challenging without long‐term continuous observations and that, for remote volcanoes like Bagana, both drones and satellite observations are powerful tools to undertake these observations. Key Points: We present the first measurements of volcanic gas composition at Bagana volcanoCO2 and SO2 fluxes at Bagana vary widely with levels of unrest, from ∼102 to ∼104 td−1Unoccupied aerial systems (drones) are of great value in monitoring emissions from inaccessible volcanic summits [ABSTRACT FROM AUTHOR]