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Anti-CD19 chimeric antigen receptor T cells (CART) has rapidly been adopted as the standard third-line therapy to treat aggressive B-cell lymphomas (ABCL) after failure of second-line therapy despite the lack of direct comparisons with allogeneic hematopoietic cell transplantation (alloHCT)-based strategies. Using the Grupo Español de Trasplante y Terapia Celular(GETH-TC) registry, we selected patients with the following characteristics: CART or alloHCT performed between 2016 and 2021; ≥18 years old; ABCL diagnosis; ≥2 lines of therapy; and either anti-CD19 CART or alloHCT as therapy at relapse. The analysis included a total of 316 (CART = 215, alloHCT = 101) patients. Median follow-up was 15 and 36 months for the CART and alloHCT cohorts, respectively. In the multivariate analysis, CART was confirmed to be similar to alloHCT for the primary study endpoint (progression-free survival) (hazard ratio [HR] 0.92, CI95%:0.56–1.51, p= 0.75). Furthermore, when the analysis was limited to only patients with chemo-sensitive diseases (complete and partial response) at infusion (CART = 26, alloHCT=93), no differences were reported (progression-free survival at month +18: 65% versus 55%, p= 0.59). However, CART had lower non-relapse mortality (HR 0.34, 95% CI: 0.13–0.85, p= 0.02). Given the lower toxicity and similar survival outcomes, these results suggest the use of CART before alloHCT.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1–5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1–10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23–67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63–89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients.

This work presents a control strategy for a leader-follower formation distance-based model of two single order kinematic model of robots. It uses feedback linearization techniques to derive the control action on the follower robot to maintain a desired distance and orientation with respect to the leader robot. Besides, it is shown that a suitable selection of the desired parameters make the formation behave as a rigid body. The control strategy is applied in a laboratory environment with two omnidirectional robots to show its performance.

This paper presents the design and analysis of three trajectory tracking control strategies for groups of unicycle-type robots using the leader-followers scheme. The leader converges asymptotically to a predefined trajectory path while the follower robots achieve a desired formation pattern at same time. The control laws are based on a dynamical extension of the kinematic model of unicycles considering the midpoint of the wheels axis of the robots as output function. When the linear velocity of unicycles is close to zero, a complementary control law is enabled momentarily to avoid singularities. It is demonstrated that in the switched closed-loop system, the orientation angles converge to the same value. Finally, some numerical simulations and real-time experiments show the performance of the control strategies.

Information on reproductive traits of semi-captive breeding of the pampas deer Ozotoceros bezoarticus arerunguaensis, an endangered species, was registered during 20 years. Birth events were monitored every 1-2 days from 1981 to 2000, and birth date, mother and father identities, sex and mass of fawns were all registered. Although births occurred throughout the year, a seasonal pattern with a peak in spring was observed. Dispersion of births throughout the year increased in multiparous females that previously gave birth four times or more. The interval between two consecutive parturitions was ~10 months, independently of the mother parity and of the sex of the fawn, but differed according to the timing of the previous birth. Individual variability in interbirth intervals was significantly higher in primiparous than in multiparous females. Hinds born in semi-captivity had their first birth earlier in their life than hinds that were originally captured (at <1 month of age) from the wild. Single fawns were observed in all but one birth, in which twins were observed. Sex ratio was not influenced by the female parity, the season, or by the father identity. Only the mother identity influenced offspring birth mass.

The partial structure 2 of the bisketal-type, tetracyclic saudin (1), an important natural product, was de novo synthesized. A key step was the Jones oxidation of the epoxide 3, which gave rise to epoxide-ring opening, followed by acetal hydrolysis, alcohol oxidation, and, finally, intramolecular acetal formation. The resulting key intermediate was finally oxidized to the target lactone 2.

Different convergent approaches to the highly oxygenated sesquiterpene natural product saudin (1), has been investigated. Our strategy has included a Michael addition and aldol condensation reaction as key steps. During the synthetic development, we have found serious steric hindrance when an α-Me-substituted alkyl vinyl ketone was used. Such steric hindrance has been overcome by synthesizing the vinyl ketone 16 through an anionic fragmentation, which was carefully studied. Finally, the intermediate 18 has been synthesized in a one-pot reaction from the vinyl ketone 16 and has been cyclized to obtain the promising tricyclic intermediate 20.

Structural, magnetic, electrochemical, EPR, 1H NMR, and H₂O₂ reactivity studies are reported for [MnIII₂(X-salpentO)(μ-AcO)(μ-MeO)(MeOH)₂]Br (1: X = 5-OMe and 2: X = 3-OMe; salpentOH = 1,5-bis(salicylidenamino)pentan-3-ol). The X-ray diffraction analysis of 2 reveals that the manganese atoms possess an axially elongated-octahedral geometry. The elongation is perpendicular to the bridging plane resulting in a short Mn⋯Mn distance of 2.9278(6) Å. The ligand lies in the meridional plane and the sixth co-ordination position of each manganese atom is occupied by a methanol molecule providing two substitution-labile sites in cis-position. Solution structural studies indicate that complexes 1 and 2 are stable in methanol and dmf, even in the presence of water, and the solid state structure is retained in solution. The two complexes show catalytic activity toward disproportionation of H₂O₂ in methanol and dmf at 25 °C. The initial rate of oxygen evolution in the presence of 1 or 2 is first order in [catalyst] and show saturation kinetics with [H₂O₂]. Complexes 1 and 2 dismutate H₂O₂ without a kinetic lag phase and are implicated as the active form of the reduced catalyst. Comparison to other dimanganese complexes of this family reveals that the methoxy phenyl-ring substituted derivatives are more effective at reducing H₂O₂ but are less efficient at binding the H₂O₂ substrate (higher K_M) than the 5-bromo or the unsubstituted complexes.

A general approach to substituted octahydrophenanthrenes was developed, which allows the stereoselective introduction of functionality at all positions. The procedure utilizes 4a-methyl-2,3,4,4a,9, 10-hexahydrophenanthrene 1, readily available from phenanthrene by reductive alkylation.

Starting from drimenol, an alternative and stereoselective synthesis of 8β(H)-drimane, a widespread occurring sesquiterpane in petroleums, is described. The epimer 8α(H)-drimane was also prepared and a comparative 13C NMR spectral analysis of both stereoisomers was carried out.

Starting from argentilactone [(5R)-(-)- δ -lactone of 5-hydroxydodeca-Z,Z-2,6-dienoic acid] and via the hydrobromic acid opening of the 65, 75-epoxide followed by acetylation and catalytic hydrogenation of the corresponding bromohydrin, (5R, 65)-(-)-erythro-6-acetoxy-5-dodecanolide was obtained. Through the 6R, 7R-epoxide and following the same sequence, the stereoisomer (5R, 6R)-(+)-threo-6-acetoxy-5-dodecanolide, was also synthesized.

The stereoselective transformation of grindelic acid, through the known methyl 6α-hydroxygrindelate, into 1-deoxy-13-epierigerol is described.

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2and CX3CR1genes influence the risk of IA in high-risk hematological patients.

1. INTRODUCTION

Introduction

This paper presents three trajectory tracking control strategies for unicycle-type robots based on a leader-followers scheme. The leader robot converges asymptotically to a smooth trajectory, while the follower robots form an undirected open-chain configuration at the same time. It is also shown that the orientation angles of all the robots converge to the same value. The control laws are based on a dynamic extension of the kinematic model of each robot. The output function to be controlled is the midpoint of the wheel axis of every robot. This choice leads to an ill-defined control law when the robot is at rest. To avoid such singularities, a complementary control law is enabled momentarily when the linear velocity of the unicycles is close to zero. Finally, numerical simulations and real-time experiments show the performance of the control strategies.