Evaluation of Sézary cell marker expression and cell death behaviour upon in vitro treatment by flow cytometry in Sézary syndrome patients.

The diagnosis of Sézary syndrome (SS) relies on the identification of blood Sézary cells (SC) by different markers via flow cytometry. Treatment of SS is challenging since its pathogenesis is characterized by cell death resistance rather than hyperproliferation. In this study, we establish an integrated approach that considers both the expression of SC markers and sensitivity to cell death both spontaneously and upon in vitro treatment. Peripheral blood mononuclear cells were isolated from 20 SS patients and analysed for the SC markers CD7 and CD26 loss as well as CD158k and PD1 gain. The cells were then treated with different established and experimental therapies in vitro and cell death was measured. Spontaneous and therapeutically induced cell death were measured and correlated to cellular marker profiles. In the marker-positive cells, spontaneous cell death sensitivity was reduced. Different treatments in vitro managed to specifically induce cell death in the putative CTCL cell populations. Interestingly, a repeated analysis after 3 months of treatment revealed the CTCL cell death sensitivity to be restored by therapy. We propose this novel integrated approach comprising the evaluation of SC marker expression and analysis of cell death sensitivity upon treatment that can also enable a better therapy stratification.

Health-related quality of life and its influencing factors in patients with primary cutaneous B-cell lymphomas: A multicentric study in 100 patients.

BACKGROUND: Primary cutaneous B-cell lymphomas (CBCL) are a group of rare malignant skin diseases that represent approximately 20%-30% of all primary cutaneous lymphomas (PCL). Previous studies revealed impaired health-related quality of life (HRQoL) in patients diagnosed with primary cutaneous T-cell lymphoma (CTCL). Currently, only small-sized studies investigated HRQoL in CBCL patients and lacked detailed analysis of respective subtypes. OBJECTIVES: This study aims to investigate HRQoL in CBCL patients to identify independent factors of HRQoL impairment in CBCL patients. METHODS: One hundred CBCL patients were recruited from eight German PCL centres in this multicentric, cross-sectional study from 2021 to 2022. The patients completed the dermatologic HRQoL questionnaire Skindex-29 and an investigator-designed 'CBCL-Questionnaire' with additional questions on HRQoL and clinical characteristics. RESULTS: The Skindex-29 revealed that HRQoL in CBCL patients is impaired on a mild to moderate level. The multiple regression analysis identified parameters like worries about dying, feeling prejudiced/discriminated and impairment of daily activities to be independently associated with impairment of HRQoL. Highest scores for HRQoL impairment were found in patients with primary cutaneous follicle centre lymphoma while on rituximab treatment and in patients with primary cutaneous marginal zone lymphoma while on watchful waiting. CONCLUSIONS: HRQoL is impaired in CBCL patients, even though, in the face of indolent disease course and favourable prognosis in the majority of cases. Of note, our investigator-designed tool identified worries about dying, feeling prejudiced/discriminated, and the type of treatment to have a negative impact on patients' HRQoL. Our study highlights the importance of a thorough patient-doctor communication to capture overall disease burden because generic HRQoL tools might lack of disease-specific items.

First-principles study of crystal structural stability and electronic and magnetic properties in LaMn(7)O(12).

The crystal structure, electronic and magnetic properties of LaMn(7)O(12) ((LaMn(3)(3+))(A)Mn(4)(3+)O(12)) are investigated by GGA (LSDA) and GGA + U (LSDA + U) (0.0 ≤ U ≤ 5.0 eV) methods. Based on two experimentally refined structures (distinguished by the distortion parameter Δ, namely S(I) (Δ = 8.5 × 10(-5)) and S(II) (Δ = 25.0 × 10(-4))), GGA and GGA + U with U < 3.0 eV calculations indicate that S(I) with a small distortion is the lowest-energy crystal structure while GGA + U with 3.0 ≤ U ≤ 5.0 eV calculations show that S(II) with a larger distortion is the ground-state crystal structure. Within the LSDA method, S(II) is always the ground-state structure no matter if U is considered or not. There are two independent magnetic sublattices: Mn(3+) within the A site and Mn(3+) within the B site. First, it is predicted that A-site Mn(3+) ions are preferably AFM-coupled in G-type (antiferromagnetically coupled in three directions). Based on this result, four magnetic configurations (FM-[Formula: see text], AFM1-[Formula: see text], AFM2-[Formula: see text] and AFM3-[Formula: see text]) are designed, and their total energies are calculated. Our results demonstrate that AFM2 and AFM3 are the lowest magnetic state, respectively, for S(I) and S(II). Correspondingly, LaMn(7)O(12) is metallic with no orbital ordering at AFM2 for S(I) while it is an insulator with orbital ordering at AFM3 for S(II). Thus, modulation of the distortion parameter Δ, e.g. by chemical doping, could be employed as a new avenue to induce a magnetic phase transition and the corresponding metal-to-insulator transition in LaMn(7)O(12).

Gigahertz modulation of GaAs-based bipolar cascade vertical cavity surface-emitting lasers.

The high-frequency modulation characteristics of GaAs-based bipolar cascade vertical cavity surface-emitting lasers operating at 980 nm with GaAs tunnel junctions and p-doped Al0.98Ga0.02As oxide apertures have been measured. We achieve -3 dB laser output modulations of 6.5 GHz for two-stage and 9.4 GHz for three-stage devices in response to small-signal current injection at an operating temperature of -50 degrees C.