BUSCADOR RECOLECTA

[Background] Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients., [Methods] 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients., [Results] Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients., [Conclusion] CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL., [Clinical trial registration] https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29., Peer reviewed

(A–B’) Stills taken from live imaging of migrating BCs from egg chambers of the indicated genotypes. Scale bar in A’ and B’, 20 μm., Peer reviewed

TG/DTG/SDTA-MS and DSC curves for the series of compounds S1 and S2, emission and excitation spectra of yttrium-based compounds Za1 and Za2, section of synthesis and structural characterization for DZa7, and X-ray crystallographic information (CIF files) for the series of compounds S1 and S2, and compound DZa7., Peer reviewed

Materials and methods: Diagnosis of VSP: Vasospasm diagnosis was performed via clinical symptoms, transcranial Doppler, or angiography between days 0 to 14 after the bleeding event. Symptomatic vasospasm was defined as worsening of the level of consciousness of ≥2 points on the Glasgow Coma Scale, or by the appearance of a focal defect (such as hemiparesis, aphasia, apraxia, hemianopia, or neglect) between days 4 and 14 after the bleeding event, not attributable to rebleeding, hematoma, hydrocephalia, metabolic alterations, infection, or oversedation. Transcranial Doppler exploration (Doppler Multidop-P, DWL) was performed with a 2-MHz ultrasound probe through the temporal window, in both hemispheres. The first study was carried out on the third day, and every day between days 3 and 14 after aSAH, and beyond this date if the transcranial Doppler recording was not normal. Transcranial Doppler vasospasm or sonographic vasospasm was defined as the mean flow velocity (MV) in any vessel of anterior cerebral circulation ≥120 cm/s. If the MV obtained reached 120 cm/s, the Lindegaard index was calculated by simultaneously recording the homolateral extracranial internal carotid artery at the submandibular site and the MV of the middle cerebral artery. The MV middle cerebral artery/MV extracranial internal carotid artery ratio of >3 was classified as sonographic vasospasm. Patients with MV >120 cm/s and Lindegaard index <3 were diagnosed with increased cerebral blood flow. Using digital subtraction angiography, angiographic vasospasm was defined as a reduction in the diameter of the cerebral artery by more than two-thirds of its baseline caliber., Supplemental Table 1. Statistical analysis of the expression of surface adhesion molecules in circulating and adherent lymphocytes and monocytes. n= 20 control subjects and 21 patients. *, **, *** P≤ 0.05, 0.01, 0.001., Supplemental Figure 1. Gating strategy for the immunocharacterization of PBMCs. (A) Identification of the cells of interest performed by SSC-A and FSC-A. (B) Singlets filter by FSC-A and FSC-H. (C) Alive cells by exclusion of 7-AAD. (D) Identification of PBMCs by SSC-A and expression of CD45. (E) Identification of lymphocytes and monocytes by SSC-A and expression of CD11b. (F) Identification of lymphocyte subpopulations by expression of CD3 and CD19., Supplemental Figure 2. Expression of surface adhesion molecules in circulating and adhered T lymphocytes and monocytes (these data are the same that are shown on Figure 4 of the manuscript, but shown patient by patient). Only statistically significant changes in the adhesion molecules are presented. Comparisons between experiments from the same patients were assessed by paired t test (* P≤ 0.05 vs. control; #P≤ 0.05 vs. P24h)., Peer reviewed

(A, A’) S9 triple>LanB1RNAi (B) egg chambers stained with anti-LanB1 antibody (green), the DNA marker Hoechst (blue) and the PC marker Fasciclin III (FasIII, red). (B–C’) Stills taken from live imaging of BCs from control (C306Gal4; slboGal4; tslGal4) and C306; slbo; tsl>LanB1RNAi egg chambers. (D) Quantification of the migration defects in egg chambers of the indicated genotypes. The statistical significance of differences was assessed with a t test. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A” and B”, 20 μm. The raw data underlying panel D are available in S1 Data., Peer reviewed

(A) Schematic drawing of an early S9 egg chamber illustrating the BCs (yellow), NCs (gray), FCs (purple), BM (green), and the position where AFM measurements were taken (arrow). (B) Comparison of the apparent elastic modulus K in egg chambers of the designated genotypes. (C) Schematic drawing of a middle S9 egg chamber illustrating the BCs (yellow), NCs (gray), FCs (purple), BM (green), the mirror region (pink square) and the positions where AFM measurements were taken, anterior to the mirr region (A, black arrow) and in the mirr region (C, pink arrow). (D, E) Comparison of the apparent elastic modulus K in the mirr region (C) and anterior to the mirr region (E), in 4 control mirrGal4 (D) and mirr>EHBP1mCh egg chambers. A minimum of 4 different readings (circles)/egg chamber were taken. Horizontal lines in B, D, and E represent mean values. The statistical significance of differences was assessed with a t test, * P value < 0.05, ** P value < 0.01, and *** P value < 0.001. Horizontal and vertical lines indicate mean and SD, respectively. The raw data underlying panels B, D, and E are available in S1 Data., Peer reviewed

(A) S10 control tjGal4 and (B) tj>LanB1RNAi (B) egg chambers stained with anti-LanB1 antibody (green), the DNA marker Hoechst (blue) and the F-actin marker Rhodamine-Phalloidin (F-actin, red). (C) Quantification of the LanB1 levels in egg chambers of the specified genotypes. The statistical significance of differences was assessed with a t test, *** P value < 0.001. Horizontal and vertical lines indicate mean and SD, respectively. Scale bars in A and B, 20 μm. The raw data underlying panel C are available in S1 Data., Peer reviewed

This dataset includes very high spatial resolution observations at 1 m spatial resolution observations of the snow depth, the NDVI and the melt-out date (DOY of year) acquired with an Unmanned Aerial Vehicle at a sub-alpine site in the Pyrenees, the Izas Experimental Catchment. During two snow seasons (2019-2020 and 2020-2021), 14 NDVI and 17 snow depth distributions were acquired over 48ha. From the snow depth observations the melt-out dates have been derived. Also information on the main topographic variables (elevation, aspect and slope) is included, with same spatial resolution, in this dataset., Peer reviewed

Supplementary material: Table S1. Summary of UAV acquisition during the study period. DOY: Julian Day of the Year.-- Table S2: Plant species observed on each survey plot.-- Figure S1: Upper panel shows, mean, minimum and maximum daily temperatures (5-day moving average). The lower panel depicts the temporal evolution of the snow depth and the total precipitation observed at the automatic weather station.-- Figure S2: Box plots depicting the temporal evolution of the NDVI for the UAV acquisition dates in the plants survey plots in 2019-2020 (upper panel) and 2020-2021 (bottom panel). The boxes show first and third quantiles and the horizontal line inside each box the second percentile (median). Whiskers of each plot include maximum and minimum values for each plot and day.-- Figure S3: Box plot (upper panel) of ASD spectrometer and Sequoia camera mounted on the UAV for the four bands and the NDVI computed from the near infrared and red bands. Linear adjustment (bottom panel) between the NDVI observations of the UAV and the ASD., Peer reviewed

BC migration in tslGFP; mirrGal4 and tslGFP; mirr> AbiRNAi egg chambers, related to Fig 6. Scale bar, 20 μm., Peer reviewed