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Background/Objectives : Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking. We performed this retrospective analysis to analyze real life outcomes in chronic lymphocytic leukemia patients receiving a combination of obinutuzumab with different chlorambucil schedules. Methods: This was a retrospective survey performed in order to analyze the feasibility and efficacy of different obinutuzumab and chlorambucil combinations in a real-life setting. Patients receiving this combination as a front-line therapy for chronic lymphocytic leukemia in participating centers, outside of clinical trials, in 2017 and 2018 were included. Results: Seventy-three patients fulfilling entry criteria were identified. Their median age was 76 years, and ranged from 58 to 90 years. The median follow up time was 59 months. The response rate was 89%, with a median progression-free survival time of 27 months, and an overall survival time of 49 months. Chlorambucil was administered as planned in 15 of the 22 (79%) patients treated with chlorambucil pulses every 2 weeks; in 15 of the 42 (34%) patients treated with 7-day courses of chlorambucil administered every 4 weeks; and in 0 of the 10 patients treated with a continuous high dose of chlorambucil ( p = 0.002). Changes in treatment schedules were made due to side effects. The progression-free and overall survival rates were similar between the three groups. Conclusions: The combinations of obinutuzumab with more intensive chlorambucil schedules are less feasible, preventing the administration of the intended higher total dose of chlorambucil, and do not improve outcomes in comparison to chlorambucil pulses administered every 2 weeks.

Background and Objectives : eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods : We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results : A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively ( p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively ( p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively ( p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) ( p = 0.98) and 5yOS 100% vs. 93.3% ( p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions : eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

The aim of this study was to investigate the creation of humic substances during biodegradation of heavy residual fuel oil, because there are indications that substances similar to humic substances are generated during biodegradation of polycyclic aromatic hydrocarbons. In the study, which lasted for 110 days, biodegradation of heavy residual fuel oil was carried out in a layer of artificial soil substrate. The initial concentration of the total petroleum hydrocarbon in the prepared artificial soil substrate (biopile) was 23.1 g kg -1 dry weight (d.w.). At the end of the process, the total petroleum hydrocarbons were reduced to 8.1 g kg -1 d.w. in the inoculated biopile, while the content of humic acids increased during bioremediation from 3.15 g kg -1 d.w. to 4.95 g kg -1 d.w. The humic acids extracted from biopile during the biodegradation process were characterized by various chemical techniques (elemental analysis, spectrofluorimetric analysis, electrochemical measurements, and size exclusion chromatography). The results showed that levels of C, H and the H/C ratio decreased as the biodegradation process progressed. This indicated that humic acids aromatization process took place and this was confirmed by the spectrofluorimetric analysis. The increase of oxygen percentage and the O/C ratio in the humic acids after the biodegradation treatment indicated an increase in functional oxygen groups. Additional analyses of humic acids from the inoculated biopile showed that they were transformed during the bioremediation process. They had greater redox and buffering capacities and a larger portion of the fractions had high molecular mass. Also, the humification parameters (the C HAs /C FAs ratio and C HAs /C org ratio) increased during the biodegradation. This is one of the few studies that describes the generation of humic substances during the biodegradation of oil compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common and most aggressive malignant primary brain tumor in humans. Clinically useful molecular markers that help predict response to therapy and prognosis are still rare. The research was conducted in 55 patients with GBM, 26 (47.3%) women and 29 (52.7%) men, mean age 62.58 years. On immunohistochemical analysis, primary antibody to CD44 (dilution 1:50) and primary antibody to endoglin (CD105) (dilution 1:250) were used to evaluate neovascularization. Statistical analysis showed negative correlation between CD44 and survival (p=0.023) (higher expression of CD44 was correlated with shorter survival), but there was no correlation between neovascularization determined by CD105 in GBM and patient survival. Thus, significant individual predictors of longer survival were lower expression of CD44 (p=0.004), higher Karnofsky score (p=0.045), and female gender (p=0.017). The results obtained suggested the possible role of CD44 in the progression and tumor neovascularization of GBM.

Model studies of prebiotic chemistry have revealed compelling routes for the formation of the building blocks of proteins and RNA, but not DNA. Today, deoxynucleotides required for the construction of DNA are produced by reduction of nucleotides catalysed by ribonucleotide reductases, which are radical enzymes. This study considers potential non-enzymatic routes via intermediate radicals for the ancient formation of deoxynucleotides. In this context, several mechanisms for ribonucleotide reduction, in a putative H2 S/HS(.) environment, are characterized using computational chemistry. A bio-inspired mechanistic cycle involving a keto intermediate and HSSH production is found to be potentially viable. An alternative pathway, proceeding through an enol intermediate is found to exhibit similar energetic requirements. Non-cyclical pathways, in which HSS(.) is generated in the final step instead of HS(.) , show a markedly increased thermodynamic driving force (ca. 70 kJ mol(-1) ) and thus warrant serious consideration in the context of the prebiotic ribonucleotide reduction., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New organic superbases have been designed using the concept of multiple intramolecular hydrogen bonds. Substituents capable of forming strong intramolecular H-bonds were selected on the basis of the energy of stabilization that occurs upon the formation of a complex between N,N',N"-trimethylguanidine and small model molecules. The proton affinities and the corresponding pK(a) values in acetonitrile of the new superbases are examined by Density Functional Theory (DFT). It is shown that N,N',N"-substitution of guanidine with appropriate substituents results in new organic superbases with gas phase proton affinities between 286 and 293 kcal mol(-1), thus being 15 to 20 kcal mol(-1) more basic than parental superbase N,N',N"-tris[(3-dimethylamino)propyl]-guanidine (tris-DMPG), whereas estimated pK(a) values in acetonitrile range between 29.5 and 33.2.