Effector T cells under hypoxia have an altered transcriptome similar to tumor-stressed T cells found in non-responsive melanoma patients.

Background: In the tumor microenvironment (TME), hypoxia stands as a significant factor that modulates immune responses, especially those driven by T cells. As T cell-based therapies often fail to work in solid tumors, this study aims to investigate the effects of hypoxia on T cell topo-distribution in the TME, gene expression association with T cell states, and clinical responses in melanoma.

Methods: To generate detailed information on tumor oxygenation and T cell accessibility, we used mathematical modeling of human melanoma tissue microarrays that incorporate oxygen supply from vessels, intratumoral diffusion, and cellular uptake.

The alternative approach to the lumbosacral segment: the right-sided OLIF compared with ALIF.

Background: Anterior lumbar interbody fusion with dorsal percutaneous pedicle screw fixation (ALIF+D) is a well-described technique treating lumbosacral degenerative diseases. Mobilising the common iliac arteries and veins (CIA and CIV) during the ALIF+D approach may increase the risk of bleeding when the bifurcations are low. This study demonstrates that in such cases, the right-sided oblique lumbar interbody fusion with dorsal percutaneous pedicle screw fixation (OLIF+D) offers a novel alternative to the ALIF+D approach.

Automated Single Cell Phenotyping of Time-of-Flight Secondary Ion Mass Spectrometry Tissue Images.

Existing analytical techniques are being improved or applied in new ways to profile the tissue microenvironment (TME) to better understand the role of cells in disease research. Fully understanding the complex interactions between cells of many different types and functions is often slowed by the intense data analysis required. Multiplexed Ion Beam Imaging (MIBI) has been developed to simultaneously characterize 50+ cell types and their functions within the TME with a subcellular spatial resolution, but this results in complex data sets that are challenging to qualitatively analyze.

Long-term tracking of social structure in groups of rats.

Rodents serve as an important model for examining both individual and collective behavior. Dominance within rodent social structures can determine access to critical resources, such as food and mating opportunities. Yet, many aspects of the intricate interplay between individual behaviors and the resulting group social hierarchy, especially its evolution over time, remain unexplored.

Multidimensional social influence drives leadership and composition-dependent success in octopus-fish hunting groups.

Collective behaviour, social interactions and leadership in animal groups are often driven by individual differences. However, most studies focus on same-species groups, in which individual variation is relatively low. Multispecies groups, however, entail interactions among highly divergent phenotypes, ranging from simple exploitative actions to complex coordinated networks.

Revealing the mechanism and function underlying pairwise temporal coupling in collective motion.

Coordinated motion in animal groups has predominantly been studied with a focus on spatial interactions, such as how individuals position and orient themselves relative to one another. Temporal aspects have, by contrast, received much less attention. Here, by studying pairwise interactions in juvenile zebrafish (Danio rerio)-including using immersive volumetric virtual reality (VR) with which we can directly test models of social interactions in situ-we reveal that there exists a rhythmic out-of-phase (i.

NKG2D receptor signaling shapes T cell thymic education.

The role of natural killer group 2D (NKG2D) in peripheral T cells as a costimulatory receptor is well established. However, its contribution to T cell thymic education and functional imprint is unknown. Here, we report significant changes in development, receptor signaling, transcriptional program, and function in T cells from mice lacking NKG2D signaling.

Targeting intracellular oncoproteins with dimeric IgA promotes expulsion from the cytoplasm and immune-mediated control of epithelial cancers.

Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied the ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific dIgA, but not IgG, neutralized KRAS within ovarian carcinoma cells and expelled this oncodriver from tumor cells.

Fine-scale collective movements reveal present, past and future dynamics of a multilevel society in Przewalski's horses.

Studying animal societies needs detailed observation of many individuals, but technological advances offer new opportunities in this field. Here, we present a state-of-the-art drone observation of a multilevel herd of Przewalski's horses, consisting of harems (one-male, multifemale groups). We track, in high spatio-temporal resolution, the movements of 238 individually identified horses on drone videos, and combine movement analyses with demographic data from two decades of population monitoring.

SMART-BARN: Scalable multimodal arena for real-time tracking behavior of animals in large numbers.

The SMART-BARN (scalable multimodal arena for real-time tracking behavior of animals in large numbers) achieves fast, robust acquisition of movement, behavior, communication, and interactions of animals in groups, within a large (14.7 meters by 6.6 meters by 3.

Sézary syndrome originates from heavily mutated hematopoietic progenitors.

The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or T-cell receptor (TCR) sequencing of 32 619 CD3+CD4+ and CD26+/CD7+ and 29 932 CD3+CD4+ and CD26-/CD7- lymphocytes from the peripheral blood of 7 patients with CTCL, coupled to single-cell ATAC-sequencing of 26,411 CD3+CD4+ and CD26+/CD7+ and 33 841 CD3+CD4+ and CD26-/CD7- lymphocytes, we show that tumor cells in Sézary syndrome and mycosis fungoides (MF) exhibit different phenotypes and trajectories of differentiation. When compared to MF, Sézary cells exhibit narrower repertoires of TCRs and exhibit clonal enrichment.

Actionable spontaneous antibody responses antagonize malignant progression in ovarian carcinoma.

Objective: To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression and can be leveraged to develop future immunotherapies.

Methods: B cells from cyopreserved clear cell ovarian carcinoma (CCC, n = 2), endometrioid ovarian carcinoma (EC, n = 2), and endometriomas (n = 2) were isolated, activated, and EBV-immortalized. Antibodies were purified from B cell supernatants and used for screening arrays containing most of the human proteome.

CCF-GNN: A Unified Model Aggregating Appearance, Microenvironment, and Topology for Pathology Image Classification.

Pathology images contain rich information of cell appearance, microenvironment, and topology features for cancer analysis and diagnosis. Among such features, topology becomes increasingly important in analysis for cancer immunotherapy. By analyzing geometric and hierarchically structured cell distribution topology, oncologists can identify densely-packed and cancer-relevant cell communities (CCs) for making decisions.

Inferring social influence in animal groups across multiple timescales.

Many animal behaviours exhibit complex temporal dynamics, suggesting there are multiple timescales at which they should be studied. However, researchers often focus on behaviours that occur over relatively restricted temporal scales, typically ones that are more accessible to human observation. The situation becomes even more complex when considering multiple animals interacting, where behavioural coupling can introduce new timescales of importance.

Anti-4-1BB immunotherapy enhances systemic immune effects of radiotherapy to induce B and T cell-dependent anti-tumor immune activation and improve tumor control at unirradiated sites.

Radiation therapy (RT) can prime and boost systemic anti-tumor effects via STING activation, resulting in enhanced tumor antigen presentation and antigen recognition by T cells. It is increasingly recognized that optimal anti-tumor immune responses benefit from coordinated cellular (T cell) and humoral (B cell) responses. However, the nature and functional relevance of the RT-induced immune response are controversial, beyond STING signaling, and agonistic interventions are lacking.

Head-tracking of freely-behaving pigeons in a motion-capture system reveals the selective use of visual field regions.

Using a motion-capture system and custom head-calibration methods, we reconstructed the head-centric view of freely behaving pigeons and examined how they orient their head when presented with various types of attention-getting objects at various relative locations. Pigeons predominantly employed their retinal specializations to view a visual target, namely their foveas projecting laterally (at an azimuth of ± 75°) into the horizon, and their visually-sensitive "red areas" projecting broadly into the lower-frontal visual field. Pigeons used their foveas to view any distant object while they used their red areas to view a nearby object on the ground (< 50 cm).

[Minimally invasive and O-arm assisted en bloc spinal tumor resections].

Background And Purpose: The en bloc resection of spinal tumors is required in primary spine tumors and in selected cases of secondary spine tumors, where the primary disease is under control and long survival time is expected. Three cases are presented, applying O-arm assisted navigation or minimally invasive anterior approaches for en bloc tumor removal.

Methods: O-arm navigation assisted osteotomies were carried out to remove a Th.

Genetic Subtyping and Phenotypic Characterization of the Immune Microenvironment and MYC/BCL2 Double Expression Reveal Heterogeneity in Diffuse Large B-cell Lymphoma.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is molecularly and clinically heterogeneous, and can be subtyped according to genetic alterations, cell-of-origin, or microenvironmental signatures using high-throughput genomic data at the DNA or RNA level. Although high-throughput proteomic profiling has not been available for DLBCL subtyping, MYC/BCL2 protein double expression (DE) is an established prognostic biomarker in DLBCL. The purpose of this study is to reveal the relative prognostic roles of DLBCL genetic, phenotypic, and microenvironmental biomarkers.

Percutaneous Spine Fusion Combined with Whole-Body Traction in the Acute Surgical Treatment of AO A- and C-Type Fractures: A Technical Note.

Background: A diminished level of pain following the operation and shortened hospitalization are the distinct advantages of minimally invasive spine surgery (MISS). However, manipulating the spine with additional MISS tools (e.g.

The geometry of decision-making in individuals and collectives.

Choosing among spatially distributed options is a central challenge for animals, from deciding among alternative potential food sources or refuges to choosing with whom to associate. Using an integrated theoretical and experimental approach (employing immersive virtual reality), we consider the interplay between movement and vectorial integration during decision-making regarding two, or more, options in space. In computational models of this process, we reveal the occurrence of spontaneous and abrupt "critical" transitions (associated with specific geometrical relationships) whereby organisms spontaneously switch from averaging vectorial information among, to suddenly excluding one among, the remaining options.

N-glycosylation structure - function characterization of omalizumab, an anti-asthma biotherapeutic product.

Omalizumab, a glycoprotein based biotherapeutics, is one of the most frequently used targeted antibody biopharmaceutical to reduce asthma exacerbations, improve lung function and reduce oral corticosteroid use. The effector function and clearance time of such glycoprotein drugs is affected by their N-glycosylation, that defines the required administration frequency to improve the quality of life in appropriately selected patients. Therefore, the glycosylation of biologics is an important critical quality attribute (CQA).

Genomic complexity is associated with epigenetic regulator mutations and poor prognosis in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma with high mutation burdens but a low response rate to immune checkpoint inhibitors. In this study, we performed targeted next-generation sequencing and fluorescent multiplex immunohistochemistry, and investigated the clinical significance and immunological effect of mutation numbers in 424 DLBCL patients treated with standard immunochemotherapy. We found that and nonsynonymous mutations (MUT) were significantly associated with increased nonsynonymous mutation numbers, and that high mutation numbers (MUT) were associated with significantly poorer clinical outcome in germinal center B-cell-like DLBCL with wild-type .

Vortex phase matching as a strategy for schooling in robots and in fish.

It has long been proposed that flying and swimming animals could exploit neighbour-induced flows. Despite this it is still not clear whether, and if so how, schooling fish coordinate their movement to benefit from the vortices shed by others. To address this we developed bio-mimetic fish-like robots which allow us to measure directly the energy consumption associated with swimming together in pairs (the most common natural configuration in schooling fish).