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Cirrhosis and liver transplantation (LT) surgery are associated with substantial alterations to the patient's coagulation status. Accurate monitoring of these changes during LT can help manage bleeding proactively and potentially reduce transfusion requirements. Unlike conventional coagulation tests (CCTs), viscoelastic monitoring (VEM) can provide an accurate, real-time, point-of-care assessment of coagulation status during LT and hence has become an invaluable tool for anesthetists and intensive care physicians. However, it remains an enigmatic subject for transplantation surgeons who are more conversant with CCTs. This review discusses the principles of VEM, provides a primer to understanding and interpreting its output, and explains how it can be used to make real-world clinical decisions during LT., (© 2021 by the American Association for the Study of Liver Diseases.)

When molecular transitions strongly couple to photon modes, they form hybrid light-matter modes called polaritons. Collective vibrational strong coupling is a promising avenue for control of chemistry, but this can be deterred by the large number of quasi-degenerate dark modes. The macroscopic occupation of a single polariton mode by excitations, as observed in Bose-Einstein condensation, offers promise for overcoming this issue. Here we theoretically investigate the effect of vibrational polariton condensation on the kinetics of electron transfer processes. Compared with excitation with infrared laser sources, the vibrational polariton condensate changes the reaction yield significantly at room temperature due to additional channels with reduced activation barriers resulting from the large accumulation of energy in the lower polariton, and the many modes available for energy redistribution during the reaction. Our results offer tantalizing opportunities to use condensates for driving chemical reactions, kinetically bypassing usual constraints of fast intramolecular vibrational redistribution in condensed phase., (© 2022. The Author(s).)

Visual odometry is the process of estimating incremental localization of the camera in 3-dimensional space for autonomous driving. There have been new learning-based methods which do not require camera calibration and are robust to external noise. In this work, a new method that do not require camera calibration called the "windowed pose optimization network" is proposed to estimate the 6 degrees of freedom pose of a monocular camera. The architecture of the proposed network is based on supervised learning-based methods with feature encoder and pose regressor that takes multiple consecutive two grayscale image stacks at each step for training and enforces the composite pose constraints. The KITTI dataset is used to evaluate the performance of the proposed method. The proposed method yielded rotational error of 3.12 deg/100 m, and the training time is 41.32 ms, while inference time is 7.87 ms. Experiments demonstrate the competitive performance of the proposed method to other state-of-the-art related works which shows the novelty of the proposed technique.

We report phase separation and liquid-crystal ordering induced by scalar activity in a system of soft repulsive spherocylinders (SRSs) of shape anisotropy L/D=5 using molecular dynamics (MD) simulations. Activity is introduced by increasing the temperature of half of the SRSs (labeled hot) while maintaining the temperature of the other half constant at a lower value (labeled cold). The difference between the two temperatures scaled by the lower temperature provides a measure of the activity. Starting from different equilibrium initial phases, we find that activity leads to segregation of the hot and cold particles. Activity also drives the cold particles through a phase transition to a more ordered state and the hot particles to a state of less order compared to the initial equilibrium state. The cold components of a homogeneous isotropic structure acquire nematic and, at higher activity, crystalline order. Similarly, the cold zone of a nematic initial state undergoes smectic and crystal ordering above a critical value of activity while the hot component turns isotropic. We find that the hot particles occupy a larger volume and exert an extra kinetic pressure, confining, compressing, and provoking an ordering transition of the cold-particle domains.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1-17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b + monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4 + and CD8 + T cells. Additionally, anti-B7-H4 antibody treatment of BBN-carcinogen bladder cancers resulted in decreased tumor size, increased CD8 + T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

The natural history of small cell lung cancer (SCLC) includes rapid evolution from chemosensitivity to chemoresistance, although mechanisms underlying this evolution remain obscure due to scarcity of post-relapse tissue samples. We generated circulating tumor cell (CTC)-derived xenografts (CDXs) from SCLC patients to study intratumoral heterogeneity (ITH) via single-cell RNAseq of chemo-sensitive and -resistant CDXs and patient CTCs. We found globally increased ITH including heterogeneous expression of therapeutic targets and potential resistance pathways, such as EMT, between cellular subpopulations following treatment-resistance. Similarly, serial profiling of patient CTCs directly from blood confirmed increased ITH post-relapse. These data suggest that treatment-resistance in SCLC is characterized by coexisting subpopulations of cells with heterogeneous gene expression leading to multiple, concurrent resistance mechanisms. These findings emphasize the need for clinical efforts to focus on rational combination therapies for treatment-naïve SCLC tumors to maximize initial responses and counteract the emergence of ITH and diverse resistance mechanisms., Competing Interests: COMPETING INTERESTS STATEMENT L.A.B. serves on advisory committees for AstraZeneca, AbbVie, GenMab, BergenBio, Pharma Mar SA, Sierra Oncology, Merck, Bristol Myers Squibb, Genentech, and Pfizer and has research support from AbbVie, AstraZeneca, GenMab, Sierra Oncology, Tolero Pharmaceuticals. J.V.H. serves on advisory committees for AstraZeneca, Boehringer Ingelheim, Exelixis, Genentech, GSK, Guardant Health, Hengrui, Lilly, Novartis, Spectrum, EMD Serono, and Synta, has research support from AstraZeneca, Bayer, GlaxoSmithKline, and Spectrum and royalties and licensing fees from Spectrum. Otherwise, there are no pertinent financial or non-financial conflicts of interest to report.

Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we use single-cell RNA sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human and mouse PDAC tumors. We corroborate the presence of myofibroblastic CAFs and inflammatory CAFs and define their unique gene signatures in vivo . Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classic costimulatory molecules. We term this cell population "antigen-presenting CAFs" and find that they activate CD4 + T cells in an antigen-specific fashion in a model system, confirming their putative immune-modulatory capacity. Our cross-species analysis paves the way for investigating distinct functions of CAF subtypes in PDAC immunity and progression. SIGNIFICANCE: Appreciating the full spectrum of fibroblast heterogeneity in pancreatic ductal adenocarcinoma is crucial to developing therapies that specifically target tumor-promoting CAFs. This work identifies MHC class II-expressing CAFs with a capacity to present antigens to CD4 + T cells, and potentially to modulate the immune response in pancreatic tumors. See related commentary by Belle and DeNardo, p. 1001 . This article is highlighted in the In This Issue feature, p. 983 ., (©2019 American Association for Cancer Research.)

Background Aims: Mesenchymal stromal cells (MSCs), derived from several tissues including bone marrow and adipose tissue, are being evaluated in clinical trials for a range of diseases. Virtually all tissues of the body contain stromal cells, yet it is unknown whether these sources are similar in phenotype and function., Methods: We have isolated stromal cells from several human tissues including bone marrow (BM-MSCs), heart (heart stroma, HS), adipose (adipose stroma, AS) and liver (liver stroma, LS) and compared the morphology, phenotype and functional properties of these stromal cell populations., Results: The cellular phenotype of each population was identical, namely, CD105+, CD73+, CD90+, CD34- and CD45-. In addition, morphology and differentiation potential were comparable. Co-culture studies revealed similar supportive potential of BM-MSCs, AS and LS with hematopoietic cells or tumor cells. In contrast, significant inhibition of proliferation of both cells types was obtained with HS, with significant loss of viability with tumor cells, demonstrating a unique functional property of HS with regard to tumor cell proliferation., Conclusions: Although stromal cells from different tissues have similar morphology and phenotype, their functional properties vary, requiring critical evaluation of stromal cells before use in non-homologous settings. HS may play a key role in inhibiting proliferation of tumor cells in the heart, providing the reason for the low occurrence of tumor development. Given the tumor-supportive property of BM-MSCs and AS, the use of these cells in cardiac tissue may result in replacement of a tumor-inhibitory stroma with a tumor-supportive microenvironment., (Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)