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The increased risk for acquiring secondary illnesses in people living with HIV (PLWH) has been associated with immune dysfunction. We have previously found that circulating monocytes from PLWH display a trained phenotype. Here, we evaluated the metabolic profile of these cells and found increased mitochondrial respiration and glycolysis of monocyte-derived macrophages (MDMs) from PLWH. We additionally found that cART shifted the energy metabolism of MDMs from controls toward increased utilization of mitochondrial respiration. Importantly, both downregulation of IKAROS expression and inhibition of the mTOR pathway reversed the metabolic profile of MDMs from PLWH and cART-treated control-MDMs. Altogether, this study reveals a very specific metabolic adaptation of MDMs from PLWH, which involves an IKAROS/mTOR-dependent increase of mitochondrial respiration and glycolysis. We propose that this metabolic adaptation decreases the ability of these cells to respond to environmental cues by "locking" PLWH monocytes in a pro-inflammatory and activated phenotype., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14 + monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals ( TNFA , IL6 , IL1B , miR-155-5p, and IDO1 ) dominate over negative feedback signals ( NCOR2 , GSN , MSC , BIN1 , and miR-146a-5p), favoring an abnormally trained phenotype. The mechanism of this reduction in negative feedback involves the attenuated expression of IKZF1, a transcription factor required for de novo synthesis of RELA during LPS-induced inflammatory responses. Furthermore, restoring IKZF1 expression in PLWH-MDMs partially reinstated expression of negative regulators of inflammation and lowered the expression of pro-inflammatory cytokines. Overall, this mechanism may provide a link between dysfunctional immune responses and susceptibility to co-morbidities in PLWH with low or undetectable viral load., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Faia, Plaisance-Bonstaff, Vittori, Wyczechowska, Lassak, Meyaski-Schluter, Reiss and Peruzzi.)

Objective: Soft tissue deformation and ruptures complicate needle placement. However, ruptures at tissue interfaces also contain information which helps physicians to navigate through different layers. This navigation task can be challenging, whenever ultrasound (US) image guidance is hard to align and externally sensed forces are superimposed by friction., Methods: We propose an experimental setup for reproducible needle insertions, applying optical coherence tomography (OCT) directly at the needle tip as well as external US and force measurements. Processing the complex OCT data is challenging as the penetration depth is limited and the data can be difficult to interpret. Using a machine learning approach, we show that ruptures can be detected in the complex OCT data without additional external guidance or measurements after training with multi-modal ground-truth from US and force., Results: We can detect ruptures with accuracies of 0.94 and 0.91 on homogeneous and inhomogeneous phantoms, respectively, and 0.71 for ex-situ tissues., Conclusion: We propose an experimental setup and deep learning based rupture detection for the complex OCT data in front of the needle tip, even in deeper tissue structures without the need for US or force sensor guiding., Significance: This study promises a suitable approach to complement a robust robotic needle placement.

Medical lasers are commonly used in interventions to ablate tumor tissue. Recently, the picosecond infrared laser has been introduced, which greatly decreases damaging of surrounding healthy tissue. Further, its ablation plume contains intact biomolecules which can be collected and analyzed by mass spectrometry. This allows for a specific chracterization of the tissue. For a precise treatment, however, a suitable guidance is needed. Further, spatial information is required if the tissue is to be characterized at different parts in the ablated area. Therefore, we propose a system which employs optical coherence tomography as the guiding imaging modality. We describe a prototypical system which provides automatic ablation of areas defined in the image data. For this purpose, we use a calibration with a robot which drives the laser fiber and collects the arising plume. We demonstrate our system on porcine tissue samples.

Robotic ultrasound guidance is promising for tracking of organ motion during radiotherapy treatments, but the radio-opaque robot and probe interfere with beam delivery. The effect on treatment plan quality can be mitigated by the use of a robot arm with kinematic redundancy, such that the robot is able to elude delivered beams during treatment by changing its configuration. However, these changes require robot motion close to the patient, lead to an increased treatment time, and require coordination with the beam delivery. We propose an optimization workflow which integrates the problem of selecting suitable robot configurations into a linear-programming-based workflow for treatment plan optimization. Starting with a large set of candidate configurations, a minimal subset is determined which provides equivalent plan quality. Our results show that, typically, six configurations are sufficient for this purpose. Furthermore, we show that optimal configurations can be reused for dose planning of subsequent patients.