Search

Introduction: The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied. Methods: We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first‐line treatment. Fifty‐five patients were evaluated again after the treatment with CIT. Results: We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1. Conclusions: CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction. [ABSTRACT FROM AUTHOR]

Titan is an ocean world with a dense atmosphere, where photochemistry produces complex organic molecules that fall to the surface. An important astrobiological question is whether this material can mix with water and form molecules of biological interest. Large impacts heat the moon's subsurface and create liquid water melt pools. A recent study investigated impacts into Titan's clathrate‐covered ice shell. Methane clathrates are stable at Titan's surface conditions and have low thermal conductivity, making them efficient insulators that can lead to steep thermal gradients and a thin stagnant lid. The authors showed that the clathrate layer thickness primarily influences the melt distribution, while its volume is governed by the impactor size. Here, we investigate the fate of melt formed during an impact into a clathrate‐covered ice shell. Our results show two different behaviors: in cases when less melt is produced, the subsurface melt pool remains close to the surface and freezes on timescales ≲25 kyr; in cases when larger volumes of melt are produced, a downward‐oriented transport of the molten material occurs. As it descends, part of the melt freezes but some may reach the ocean within a few kyr under certain conditions; vertical impacts, high surface porosity, low viscosity, and tidal heating all favor this surface‐to‐ocean exchange. While providing insights on parameters that allow a subsurface melt pool to remain liquid beneath a Selk‐sized crater for a few kyr, this study suggests that Dragonfly may be able to sample melt deposits where organics reacted with liquid water to produce biomolecules. Plain Language Summary: Titan, Saturn's largest moon, harbors a subsurface ocean beneath its ice shell. The moon also has an atmosphere, which is rich in large organic molecules that settle onto its surface. When atmospheric methane reacts with surface water ice, it forms methane clathrate. A clathrate layer atop Titan's ice shell affects the formation of Titan's impact craters, as it is both stronger than ice and a better insulator. Here, we study the effect of this clathrate layer on the formation and subsequent fate of melt pools produced by impacts on Titan. We investigate whether the melt descends through the ice shell to reach the ocean or remains near the surface and freezes. Our results show only a limited range of scenarios where impact melt reaches the ocean. In the majority of models, impact melt freezes near the surface within short timescales, ranging from a few thousands to tens of thousands of years. This implies that surface organic molecules may have interacted with subsurface melt pools. These results provide a positive outlook for NASA's Dragonfly mission, which will explore Titan's Selk crater in search of organic materials that have reacted with water to potentially form molecules of biological interest. Key Points: We studied the evolution of impact melt pools in Titan's ice shell using numerical simulations of two‐phase thermal convectionWhile most melt pools never reach the ocean, we observe surface‐to‐ocean exchange in a small part of the investigated parameter spaceOur results suggest that Dragonfly may be able to sample melt deposits where organics reacted with liquid water to produce biomolecules [ABSTRACT FROM AUTHOR]

Background: In chronic lymphocytic leukemia (CLL), changes in the peripheral blood lymphocyte subsets play an important role in disease progression and infectious complications. The impact of chemoimmunotherapy (CIT) on these changes has not been extensively studied Methods: We used multi‐color flow cytometry, to prospectively measure absolute and relative numbers of CD4+ and CD8+ T‐cells and their subsets in 45 patients with indolent untreated CLL, 86 patients indicated for first‐line treatment, and 34 healthy controls. In 55 patients, we analyzed the impact of CIT Results: CLL patients had a significant increase in most cell populations in comparison to controls. Progression of CLL was characterized by significantly elevated counts with the exception of a lower percentage of naïve T‐cells. After treatment, the percentage of naïve T‐cells further decreased at the expense of effector memory T‐cells (TEM). In patients with indolent CLL, higher percentages of naïve CD4+ (p = 0.0026) and naïve CD8+ (p = 0.023) T‐cells were associated with a longer time to first treatment (TTFT). The elevation of CD4+ central memory T‐cells (TCM) (p = 0.27) and TEM (p = 0.003) counts and a higher percentage of CD4+ TEM (p = 0.0047), were linked with shorter TTFT. In treated patients, increased regulatory T‐cells count was associated with shorter time to next treatment (TTNT) (p = 0.042), while higher CD4+ TCM count with shorter TTNT (p = 0.035) and shorter overall survival (p = 0.041). Conclusion: Our results indicate that naïve cell depletion and CD4+ TCM and TEM increases are detrimental to CLL patients' prognosis. [ABSTRACT FROM AUTHOR]

Enceladus is a dynamic icy moon of Saturn and a leading target for future planetary missions focused on the search for life beyond Earth. For such missions, instruments that can provide geophysical and geochemical context for ice shell and ocean processes are critical to evaluate whether conditions are suitable for life and biosignature detection. Radar sounding is a powerful geophysical technique to probe the thermophysical and chemical properties of icy moons, like Enceladus, and to investigate the subsurface context for the exchange of material and energy between their subsurface oceans, ice shells, and plumes. To inform the scientific potential and instrument performance demands of such a radar‐sounding investigation of Enceladus' ice shell, we adapt and extend previous radar attenuation analysis done for Europa to the configuration and conditions of Enceladus. We also discuss how attenuation (both as an obstacle for the detection of ice shell reflectors and as a signal itself) can help constrain the thermal, physical, and chemical configuration of Enceladus' ice shell and reveal the processes governing the moon's ocean/shell/plume system. Plain Language Summary: Enceladus, a tiny icy moon of Saturn, has been attracting attention since the discovery of its spectacular water jet activity. The jets, sampling the moon's hidden deep ocean, have revealed conditions favorable for the existence of life below the cold outer ice shell. Understanding the long‐term persistence of the ocean, the jets, and their connection to the ice shell and ocean requires reliable knowledge of the shell's physical, thermal, and chemical properties. Ice penetrating radar is a powerful tool for studying ice shells in the planned missions to Jupiter's icy moons. In this paper, we expand and adapt the radar‐based approach to Enceladus in light of the established constraints on the shell's structure and chemistry. We find that although the shell's chemical composition makes direct radar detection of the ice‐ocean interface challenging, the shell's thermal structure enables constraining the thickness—and potentially chemistry—by future missions using echoes from water within the shell. Key Points: We explore radar attenuation within Enceladus' ice shell as a function of its chemistry using a 3D model of its shape and thermal structureDirect radar detection of the ice‐ocean interface is improbable for chloride‐rich shells except for the thin south‐polar regionThe NH3 eutectic isotherm is a comparatively easy‐to‐detect interface, with the potential to constrain the shell thickness and composition [ABSTRACT FROM AUTHOR]

Within the theory of interacting continua, we develop a model for a heat conducting mixture of two interacting fluids described in terms of the densities and the velocities for each fluid and the temperature field for the mixture as a whole. We use a general thermodynamic framework that determines the response of the material from the knowledge of two pieces of information, namely how the material stores the energy and how the entropy is produced. This information is expressed in the form of the constitutive equations for two scalars: the Helmholtz free energy and the entropy production. Additionally, we follow the goal to determine the response of a mixture from a small (minimal) set of material parameters, including shear viscosity, bulk viscosity and heat conductivity associated with the mixture as a whole and the drag coefficient connected with the interaction force between the constituents. The same thermodynamic approach is used to obtain the model when the mixture as a whole responses as an incompressible material. For both the compressible and incompressible mixtures, we investigate three variants stemming from different definitions of the (averaged) velocity associated with the mixture as a whole. We also address the issue of identification of boundary conditions for the individual constituents from the standard boundary conditions formulated in terms of the quantities associated with the mixture as a whole. Within the theory of interacting continua, we develop a model for a heat conducting mixture of two interacting fluids described in terms of the densities and the velocities for each fluid and the temperature field for the mixture as a whole. We use a general thermodynamic framework that determines the response of the material from the knowledge of two pieces of information, namely how the material stores the energy and how the entropy is produced. This information is expressed in the form of the constitutive equations for two scalars: the Helmholtz free energy and the entropy production.... [ABSTRACT FROM AUTHOR]