FAM3C/
I
nterleukin-
l
ike
E
MT
I
nducer (ILEI) is an oncogenic member of the FAM3 cytokine family and serves essential roles in both epithelial-mesenchymal transition (EMT) and breast cancer metastasis. ILEI expression levels are regulated through a non-canonical TGFβ signaling pathway by 3’-UTR-mediated translational silencing at the mRNA level by hnRNP E1. TGFβ stimulation or silencing of hnRNP E1 increases ILEI translation and induces an EMT program that correlates to enhanced invasion and migration. Recently, EMT has been linked to the formation of breast cancer stem cells (BCSCs) that confer both tumor cell heterogeneity as well as chemoresistant properties. Herein, we demonstrate that hnRNP E1 knockdown significantly shifts normal mammary epithelial cells to mesenchymal BCSCs
in vitro
and
in vivo
. We further validate that modulating ILEI protein levels results in the abrogation of these phenotypes, promoting further investigation into the unknown mechanism of ILEI signaling that drives tumor progression. We identify LIFR as the receptor for ILEI, which mediates signaling through STAT3 to drive both EMT and BCSC formation. Reduction of either ILEI or LIFR protein levels results in reduced tumor growth, fewer tumor initiating cells and reduced metastasis within the hnRNP E1 knock-down cell populations
in vivo
. These results reveal a novel ligand-receptor complex that drives the formation of BCSCs and represents a unique target for the development of metastatic breast cancer therapies.
Background
Current methods of communication between the point of injury and receiving medical facilities rely on verbal communication, supported by brief notes and the memory of the field medic. This communication can be made more complete and reliable with technologies that automatically document the actions of field medics. However, designing state-of-the-art technology for military field personnel and civilian first responders is challenging due to the barriers researchers face in accessing the environment and understanding situated actions and cognitive models employed in the field.
Objective
To identify design insights for an automated sensing clinical documentation (ASCD) system, we sought to understand what information is transferred in trauma cases between prehospital and hospital personnel, and what contextual factors influence the collection, management, and handover of information in trauma cases, in both military and civilian cases.
Methods
Using a multi-method approach including video review and focus groups, we developed an understanding of the information needs of trauma handoffs and the context of field documentation to inform the design of an automated sensing documentation system that uses wearables, cameras, and environmental sensors to passively infer clinical activity and automatically produce documentation.
Results
Comparing military and civilian trauma documentation and handoff, we found similarities in the types of data collected and the prioritization of information. We found that military environments involved many more contextual factors that have implications for design, such as the physical environment (eg, heat, lack of lighting, lack of power) and the potential for active combat and triage, creating additional complexity.
Conclusions
An ineffectiveness of communication is evident in both the civilian and military worlds. We used multiple methods of inquiry to study the information needs of trauma care and handoff, and the context of medical work in the field. Our findings informed the design and evaluation of an automated documentation tool. The data illustrated the need for more accurate recordkeeping, specifically temporal aspects, during transportation, and characterized the environment in which field testing of the developed tool will take place. The employment of a systems perspective in this project produced design insights that our team would not have identified otherwise. These insights created exciting and interesting challenges for the technical team to resolve.
Rhinovirus (RV)-specific surveillance studies in the Middle East are limited.Therefore, we aimed to study the clinical characteristics, outcomes, and seasonality of RV-associated acute respiratory infection among hospitalized young children in Jordan. We conducted a prospective viral surveillance study and enrolled children <2 years old admitted to a large public hospital in Amman, Jordan (2010)(2011)(2012)(2013).Demographic and clinical data were collected by structured interviews and chart abstractions. Nasal and/or throat swabs were collected and tested for a panel of respiratory viruses, and RV genotyping and speciation was performed. At least one virus was detected in 2641/3168 children (83.4%). RV was the second most common virus detected (n = 1238; 46.9%) and was codetected with another respiratory virus in 730 cases (59.0%). Children with RV codetection were more likely than those with RV-only detection to have respiratory distress but had similar outcomes. RV-A accounted for about half of RV-positive cases (54.7%), while children with RV-C had a higher frequency of wheezing and reactive airway disease.RV was detected year-round and peaked during winter. In conclusion, though children with RV codetection had worse clinical findings, neither codetection nor species affected most clinical outcomes.
Compared to adults, the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) illness in children has been lower and less severe. However, reports comparing SARS‐CoV‐2 infection among children and adults are limited. As part of our longitudinal cohort study of adults and children with SARS‐CoV‐2 infection and their household contacts in Nashville, Tennessee, we compared the clinical characteristics and outcomes of SARS‐CoV‐2 infections between children and adults. Children were more likely to be asymptomatically infected and had a shorter illness duration compared to adults. The differences observed in clinical presentation across ages may inform symptom‐specific testing, screening, and management algorithms.
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