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Additional Material 2: Mask frame assembly, donning, and seal check instructions with accompanying diagrams.

Additional file 2: Attributes of masks undergoing filtration efficiency testing including manufacturer and model, relevant regulatory standard, shape, presence of exhalation valve, type of tethering device, weight, thickness, and a picture of each mask. Mask numbers correspond to label numbers on Fig. 3 and on the first column of Additional file 4.

Purpose: Identifying intravenous (IV) contrast use within CT scans is a key component of data curation for model development and testing. Currently, IV contrast is poorly documented in imaging metadata and necessitates manual correction and annotation by clinician experts, presenting a major barrier to imaging analyses and algorithm deployment. We sought to develop and validate a convolutional neural network (CNN)-based deep learning (DL) platform to identify IV contrast within CT scans. Methods: For model development and evaluation, we used independent datasets of CT scans of head, neck (HN) and lung cancer patients, totaling 133,480 axial 2D scan slices from 1,979 CT scans manually annotated for contrast presence by clinical experts. Five different DL models were adopted and trained in HN training datasets for slice-level contrast detection. Model performances were evaluated on a hold-out set and on an independent validation set from another institution. DL models was then fine-tuned on chest CT data and externally validated on a separate chest CT dataset. Results: Initial DICOM metadata tags for IV contrast were missing or erroneous in 1,496 scans (75.6%). The EfficientNetB4-based model showed the best overall detection performance. For HN scans, AUC was 0.996 in the internal validation set (n = 216) and 1.0 in the external validation set (n = 595). The fine-tuned model on chest CTs yielded an AUC: 1.0 for the internal validation set (n = 53), and AUC: 0.980 for the external validation set (n = 402). Conclusion: The DL model could accurately detect IV contrast in both HN and chest CT scans with near-perfect performance.

Additional Material 1: Individual participant data used to construct Tables 1 and 2.

Additional file 3: NIOSH infographic illustrating the correct labeling of N95 masks.

Additional file 3: NIOSH infographic illustrating the correct labeling of N95 masks.

SUMMARY The need to test anticancer drugs in multiple indications has been addressed by basket trials, which are Phase I or II clinical trials involving multiple tumor subtypes and a single master protocol. Basket trials typically involve few patients per type, making it challenging to rigorously compare responses across types. We describe the use of permutation testing to test for differences among subgroups using empirical null distributions and the Benjamini-Hochberg procedure to control for false discovery. We apply the approach retrospectively to tumor-volume changes and progression-free survival in published basket trials for neratinib, larotrectinib, pembrolizumab, and imatinib and uncover examples of therapeutic benefit missed by conventional binomial testing. For example, we identify an overlooked opportunity for use of neratinib in lung cancers carrying ERBB2 Exon 20 mutations. Permutation testing can be used to design basket trials but is more conservatively introduced alongside established approaches to enrollment such as Simon’s two-stage design., Graphical Abstract, In Brief Basket clinical trials simultaneously test a single drug in multiple tumor subtypes, but statistical challenges limit the comparison of responses across subtypes. We describe a rigorous approach to permutation testing using empirical null distributions that can identify previously overlooked opportunities for use of targeted therapy in genetically defined cancer subtypes.

Physiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors. Computational analysis of the resulting data-sets elucidated communication-independent and communication-dependent contributions, including both positive and negative synergies. We find that cytokines in cell supernatants were uncorrelated to those found in plasma. Additionally, as an example of positive synergy, production levels of CXCR3 cytokines IP-10 and MIG, depend non-linearly on both IFNγ and TNFα levels in cross-talk between T cells and monocytes. Overall, this work demonstrates that communication between cell types can significantly impact the consequent cytokine environment, emphasizing the value of mixed cell population studies., United States. National Institutes of Health (DP3 DK097681), Institute for Collaborative Biotechnologies (W911NF-09-0001), David H. Koch Institute for Integrative Cancer Research at MIT, National Science Foundation (U.S.)