Impact of FGFR2 gene fusions on survival of patients with intrahepatic cholangiocarcinoma following curative intent resection.

BACKGROUND: Intrahepatic Cholangiocarcinoma (iCCA) is an aggressive cancer with diverse mutational profiles. An important molecular subtype is fibroblast growth factor receptor 2 (FGFR2) fusion. The effect of FGFR2 fusions on prognosis is unknown. Our aim was to assess the outcomes in resected CCA patients in relation to FGFR2 status. METHODS: Surgically treated CCA patients from a single institution were retrospectively reviewed between 2008 and 2014. FGFR rearrangements were detected by fluorescence in situ hybridization (FISH). Data included patient demographics, tumor pathology, disease-free survival (DFS) and overall survival (OS). RESULTS: Ninety-five patients underwent surgical resection for iCCA. Twelve (13%) of these were found to have FGFR2 fusion, none of which were treated with FGFR targeted therapy. Patients with FGFR2 fusions were found to have a longer 5-year (83 vs. 32%, p = 0.01) and 10-year (46 vs. 22%, p = 0.04) OS. Five and 10-year DFS was also increased (68 vs. 33% p = 0.04) and (68 vs. 25 %, p = 0.02,). FGFR2 fusion status was the strongest independent factor associated with improved OS (HR 0.23, 0.09-0.62, p=0.003) and DFS (HR 0.18, 0.05-0.67, p=0.01). CONCLUSION: Patients with CCA FGFR2 fusion have improved OS and DFS following surgical resection.

Robot-Enabled Support of Daily Activities in Smart Home Environments.

Smart environments offer valuable technologies for activity monitoring and health assessment. Here, we describe an integration of robots into smart environments to provide more interactive support of individuals with functional limitations. RAS, our Robot Activity Support system, partners smart environment sensing, object detection and mapping, and robot interaction to detect and assist with activity errors that may occur in everyday settings. We describe the components of the RAS system and demonstrate its use in a smart home testbed. To evaluate the usability of RAS, we also collected and analyzed feedback from participants who received assistance from RAS in a smart home setting as they performed routine activities.

Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic altered access to healthcare by decreasing the number of patients able to receive preventative care and cancer screening. We hypothesized that, given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. STUDY DESIGN: This is a retrospective cross-sectional study of 2017 to September 2021 UMass Memorial Tumor Registry data for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as before and during COVID-19. RESULTS: There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred during the time of this study compared with prepandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A nonstatistically significant decrease in lung cancer presentation was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. CONCLUSIONS: In the 2 years after the COVID-19 pandemic, we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial 2 years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia.

Circadian Structural Plasticity Drives Remodeling of E Cell Output.

Behavioral outputs arise as a result of highly regulated yet flexible communication among neurons. The Drosophila circadian network includes 150 neurons that dictate the temporal organization of locomotor activity; under light-dark (LD) conditions, flies display a robust bimodal pattern. The pigment-dispersing factor (PDF)-positive small ventral lateral neurons (sLNv) have been linked to the generation of the morning activity peak (the "M cells"), whereas the Cryptochrome (CRY)-positive dorsal lateral neurons (LNds) and the PDF-negative sLNv are necessary for the evening activity peak (the "E cells") [1, 2]. While each group directly controls locomotor output pathways [3], an interplay between them along with a third dorsal cluster (the DN1ps) is necessary for the correct timing of each peak and for adjusting behavior to changes in the environment [4-7]. M cells set the phase of roughly half of the circadian neurons (including the E cells) through PDF [5, 8-10]. Here, we show the existence of synaptic input provided by the evening oscillator onto the M cells. Both structural and functional approaches revealed that E-to-M cell connectivity changes across the day, with higher excitatory input taking place before the day-to-night transition. We identified two different neurotransmitters, acetylcholine and glutamate, released by E cells that are relevant for robust circadian output. Indeed, we show that acetylcholine is responsible for the excitatory input from E cells to M cells, which show preferential responsiveness to acetylcholine during the evening. Our findings provide evidence of an excitatory feedback between circadian clusters and unveil an important plastic remodeling of the E cells' synaptic connections.