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1. Whole blood transcriptomics identifies subclasses of pediatric septic shock

   https://doi.org/10.1186/s13054-023-04689-y  

   Yang, Jamie O. ; Zinter, Matt S. ; Pellegrini, Matteo ; Wong, Man Yee ; Gala, Kinisha ; Markovic, Daniela ; Nadel, Brian ; Peng, Kerui ; Do, Nguyen ; Mangul, Serghei ; et al ( December 2023 , Critical Care)

   Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles.

   The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses.

   Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires.

   Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences.

   Trial RegistrationThis is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

    

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2. Point‐of‐critical‐care diagnostics for sepsis enabled by multiplexed micro and nano sensing technologies

   https://doi.org/10.1002/wnan.1701  

   Ashley, Brandon K. ; Hassan, Umer ( March 2021 , WIREs Nanomedicine and Nanobiotechnology)

   Sepsis is responsible for the highest economic and mortality burden in critical care settings around the world, prompting the World Health Organization in 2018 to designate it as a global health priority. Despite its high universal prevalence and mortality rate, a disproportionately low amount of sponsored research funding is directed toward diagnosis and treatment of sepsis, when early treatment has been shown to significantly improve survival. Additionally, current technologies and methods are inadequate to provide an accurate and timely diagnosis of septic patients in multiple clinical environments. For improved patient outcomes, a comprehensive immunological evaluation is critical which is comprised of both traditional testing and quantifying recently proposed biomarkers for sepsis. There is an urgent need to develop novel point‐of‐care, low‐cost systems which can accurately stratify patients. These point‐of‐critical‐care sensors should adopt a multiplexed approach utilizing multimodal sensing for heterogenous biomarker detection. For effective multiplexing, the sensors must satisfy criteria including rapid sample to result delivery, low sample volumes for clinical sample sparring, and reduced costs per test. A compendium of currently developed multiplexed micro and nano (M/N)‐based diagnostic technologies for potential applications toward sepsis are presented. We have also explored the various biomarkers targeted for sepsis including immune cell morphology changes, circulating proteins, small molecules, and presence of infectious pathogens. An overview of different M/N detection mechanisms are also provided, along with recent advances in related nanotechnologies which have shown improved patient outcomes and perspectives on what future successful technologies may encompass.

   This article is categorized under:

   Diagnostic Tools > Biosensing

    

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3. Time-Aware Subgroup Matrix Decomposition: Imputing Missing Data Using Forecasting Events

   Yang, X. Yuan ( January 2018 , IEEE International Conference on Big Data)

   Deep neural network models, especially Long Short Term Memory (LSTM), have shown great success in analyzing Electronic Health Records (EHRs) due to their ability to capture temporal dependencies in time series data. When applying the deep learning models to EHRs, we are generally confronted with two major challenges: high rate of missingness and time irregularity. Motivated by the original PACIFIER framework which utilized matrix decomposition for data imputation, we applied and further extended it by including three components: forecasting future events, a time-aware mechanism, and a subgroup basis approach. We evaluated the proposed framework with real-world EHRs which consists of 52,919 visits and 4,224,567 events on a task of early prediction of septic shock. We compared our work against multiple baselines including the original PACIFIER using both LSTM and Time-aware LSTM (T-LSTM). Experimental results showed that our proposed framework significantly outperformed all competitive baseline approaches. More importantly, the extracted interpretative latent patterns from subgroups could shed some lights for clinicians to discover the progression of septic shock patients. 

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4. Precise measurements of self-absorbed rising reverse shock emission from gamma-ray burst 221009A

   https://doi.org/10.1038/s41550-023-01997-9  

   Bright, Joe S. ; Rhodes, Lauren ; Farah, Wael ; Fender, Rob ; van der Horst, Alexander J. ; Leung, James K. ; Williams, David R. ; Anderson, Gemma E. ; Atri, Pikky ; DeBoer, David R. ; et al ( August 2023 , Nature Astronomy)

   The deaths of massive stars are sometimes accompanied by the launch of highly relativistic and collimated jets. If the jet is pointed towards Earth, we observe a ‘prompt’ gamma-ray burst due to internal shocks or magnetic reconnection events within the jet, followed by a long-lived broadband synchrotron afterglow as the jet interacts with the circumburst material. While there is solid observational evidence that emission from multiple shocks contributes to the afterglow signature, detailed studies of the reverse shock, which travels back into the explosion ejecta, are hampered by a lack of early-time observations, particularly in the radio band. We present rapid follow-up radio observations of the exceptionally bright gamma-ray burst GRB 221009A that reveal in detail, both temporally and in frequency space, an optically thick rising component from the reverse shock. From this, we are able to constrain the size, Lorentz factor and internal energy of the outflow while providing accurate predictions for the location of the peak frequency of the reverse shock in the first few hours after the burst. These observations challenge standard gamma-ray burst models describing reverse shock emission.

    

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5. Shock Cooling and Possible Precursor Emission in the Early Light Curve of the Type II SN 2023ixf

   https://doi.org/10.3847/2041-8213/ace4c4  

   Hosseinzadeh, Griffin ; Farah, Joseph ; Shrestha, Manisha ; Sand, David J. ; Dong 董, Yize 一泽 ; Brown, Peter J. ; Bostroem, K. Azalee ; Valenti, Stefano ; Jha, Saurabh W. ; Andrews, Jennifer E. ; et al ( August 2023 , The Astrophysical Journal Letters)

   We present the densely sampled early light curve of the Type II supernova (SN) 2023ixf, first observed within hours of explosion in the nearby Pinwheel Galaxy (Messier 101; 6.7 Mpc). Comparing these data to recently updated models of shock-cooling emission, we find that the progenitor likely had a radius of 410 ± 10R_⊙. Our estimate is model dependent but consistent with a red supergiant. These models provide a good fit to the data starting about 1 day after the explosion, despite the fact that the classification spectrum shows signatures of circumstellar material around SN 2023ixf during that time. Photometry during the first day after the explosion, provided almost entirely by amateur astronomers, does not agree with the shock-cooling models or a simple power-law rise fit to data after 1 day. We consider the possible causes of this discrepancy, including precursor activity from the progenitor star, circumstellar interaction, and emission from the shock before or after it breaks out of the stellar surface. The very low luminosity (−11 mag >M> −14 mag) and short duration of the initial excess lead us to prefer a scenario related to prolonged emission from the SN shock traveling through the progenitor system.

    

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