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Graft failure (GF) is an extremely rare complication of autologous hematopoietic stem cell transplantation (auto-HSCT) with a frequency not exceeding 3–5 % of all cases of this technology. Primary graft failure is distinguished when restoration of hematopoiesis has not occurred by day +28 after hematopoietic stem cell transfusion, and secondary GF, implying the occurrence of neutropenia

Background. Post-registration observational studies with switching therapy from the original drug to a biosimilar for non-medical indications allow us to assess the safety and effectiveness of this type of switching in real clinical practice. Aim. Evaluation of the safety and effectiveness of non-medical switching from the original drug Keytruda® to the biosimilar drug Pembroria® in patients with various oncological pathologies in real clinical practice (REFLECTION). Materials and methods. A retrospective analysis of data from electronic medical records from 21 medical institutions of the Russian Federation for the period 2020–2023 was carried out. Data were included from patients with cancer of various locations who received at least 2 injections of Keytruda® followed by switching to Pembroria® for non-medical indications (at least 2 injections). Primary criteria: incidence of immune-mediated adverse reactions (ImARs) of any severity. Secondary indicators: incidence of ImARs of various degrees of severity and infusion reactions, frequency of objective response rate (according to RECIST 1.1 criteria). Results. The analysis included data from 382 patients (male/female 200/182, median age 62 years) with NSCLC (24.1%), RCC (23.3%), melanoma (20.4%) and cancer of other localization. Patients received Keytruda® on 1st and 2nd lines (54.2 and 25.4% of patients, respectively), on 3 or 4 lines (14.1%), or as part of adjuvant therapy (6.3%). 50.5% of patients received pembrolizumab as monotherapy. The median number of administrations was 7.0 and 5.0 for Keytruda® and Pembroria®, respectively. ImARs were registered in 44 (11.5%) patients (60 ImARs), including 40 ImARs in 35 (9.2%) patients while using Keytruda® and 20 ImARs in 17 (2.4%) patients with Pembroria®. The most common ImARs were hypothyroidism, hyperthyroidism, and hepatitis; the frequency of these ImARs was higher with Keytruda® (EAER for hypothyroidism 0.00422 and 0.00144, for hepatitis – 0.00124 and 0.00096, respectively). All 5 reported cases of hyperthyroidism in patients on Keytruda® (EAER 0.00124), were resolved before switching to Pembroria®. No infusion-related reactions or deaths due to ImARs have been reported. The objective response rate was comparable – 104 (32.6%) and 90 (29.2%) patients оn Keytruda® and Pembroria® therapy, respectively. Most patients maintained disease control after switching to Pembroria® [progression was recorded in 29 (9.4%) patients after switching to a biosimilar]. Conclusion. The safety profiles of Keytruda® and Pembroria® were satisfactory and comparable in this study. Switching from therapy with Keytruda® to Pembroria® is not accompanied by an increase in the frequency or severity of ImARs. Switching from Keytruda® to Pembroria® maintains disease control in most patients.

Seaweed aquaculture is gaining traction globally as a solution to many climate issues. However, seaweeds themselves are also under threat of anthropogenically driven climate change. Here, we summarize climate-related challenges to the seaweed aquaculture industry, with a focus on the developing trade in the North Atlantic. Specifically, we summarize three main challenges: i) abiotic change; ii) extreme events; and iii) disease & herbivory. Abiotic change includes negative effects of ocean warming and acidification, as well as altered seasonality due to ocean warming. This can lower biomass yield and change biochemical composition of the seaweeds. Extreme events can cause considerable damage and loss to seaweed farms, particularly due to marine heatwaves, storms and freshwater inputs. Seaweed diseases have a higher chance of proliferating under environmentally stressful conditions such as ocean warming and decreased salinity. Herbivory causes loss of biomass but is not well researched in relation to seaweed aquaculture in the North Atlantic. Despite challenges, opportunities exist to improve resilience to climate change, summarized in three sections: i) future proof site selection; ii) advances in breeding and microbiome manipulation; and iii) restorative aquaculture. We present a case study where we use predictive modelling to illustrate suitable habitat for seaweed cultivation in the North Atlantic under future ocean warming. Notably, there was a large loss of suitable habitat for cultivating Alaria esculenta and Laminaria digitata. We show how selection and priming and microbe inoculates may be a cost-effective and scalable solution to improve disease- and thermal tolerance. Co-cultivation of seaweeds may increase both yield and biodiversity co-benefits. Finally, we show that aquaculture and restoration can benefit from collaborating on nursery techniques and push for improved legislation.

Abstract Background In addition to the other uses for macroalgae, since the 1970s, there has been interest in using macroalgae as a source of biofuels, due to the high rates of productivity and intrinsic advantages over other biofuel crops such as not requiring land use or significant freshwater input. A wide range of conversion processes exist but anaerobic digestion was one of the first demonstrated and is still a widely proposed conversion pathway. To be economically viable and scalable within Europe, the industry will need to be based on a small number of fast growing, high-yielding European macroalgae species. There is a wide body of scientific work on the conversion of seaweeds to biofuel via anaerobic digestion. Main text These studies demonstrate that the efficiency of this conversion pathway is highly variable between species, processing techniques, composition and digestor conditions. In this paper, we review this body of work specifically linking it to candidate species for European macroalgae bio-energy cultivation with the aim to promote the future development of the European macroalgal cultivation sector and allow for a better alignment with the requirements for biofuel production from macroalgae. Conclusions Overall, anaerobic digestion of seaweed offers opportunities for large-scale energy production which avoids some of the issues that have faced previous generations of biofuels, but there are a number of key challenges to overcome to ensure wider adoption and economic viability. (1) Optimising the biomass production to ensure an economic and uniform feedstock with the composition optimised to increase desirable characteristics such as sugar content and the carbon and nitrogen ratio and to reduce inhibitory factors such as halogenated secondary metabolites, sulphur and heavy metals. (2) Improving conversion rates through co-digestion, pre-treatments and tailored microbial communities, using scalable and economically feasible technology. (3) Developing tailored microbial communities capable of utilising the diverse polysaccharides in seaweed feedstock and being tolerant of the saline conditions associated with them. Addressing these issues will deliver significant benefits towards the development of a bio-energy industry based on the anaerobic digestion of cultured seaweeds.

Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety. Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM. Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package. Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab. Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.

BackgroundThere is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus.MethodsIn this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with

IntroductionThe role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.MethodsIn this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests.ResultsSixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.

Seaweed aquaculture is gaining traction globally as a solution to many climate issues. However, seaweeds themselves are also under threat of anthropogenically driven climate change. Here, we summarize climate-related challenges to the seaweed aquaculture industry, with a focus on the developing trade in the North Atlantic. Specifically, we summarize three main challenges: i) abiotic change; ii) extreme events; and iii) disease & herbivory. Abiotic change includes negative effects of ocean warming and acidification, as well as altered seasonality due to ocean warming. This can lower biomass yield and change biochemical composition of the seaweeds. Extreme events can cause considerable damage and loss to seaweed farms, particularly due to marine heatwaves, storms and freshwater inputs. Seaweed diseases have a higher chance of proliferating under environmentally stressful conditions such as ocean warming and decreased salinity. Herbivory causes loss of biomass but is not well researched in relation to seaweed aquaculture in the North Atlantic. Despite challenges, opportunities exist to improve resilience to climate change, summarized in three sections: i) future proof site selection; ii) advances in breeding and microbiome manipulation; and iii) restorative aquaculture. We present a case study where we use predictive modelling to illustrate suitable habitat for seaweed cultivation in the North Atlantic under future ocean warming. Notably, there was a large loss of suitable habitat for cultivating Alaria esculenta and Laminaria digitata. We show how selection and priming and microbe inoculates may be a cost-effective and scalable solution to improve disease- and thermal tolerance. Co-cultivation of seaweeds may increase both yield and biodiversity co-benefits. Finally, we show that aquaculture and restoration can benefit from collaborating on nursery techniques and push for improved legislation. [ABSTRACT FROM AUTHOR]

A dense concentration of old-growth forest and a wet, cold climate promote mineral weathering and leaching in coastal temperate rainforest soils. Our objective was to assess soil development and soil organic carbon (SOC) distribution across 18 soil profiles in remote, upland terrain of southeast Alaska where pedon data are sparse. We made soil morphological observations, collected samples, and completed laboratory analyses to measure SOC content, pH, and particle size distribution. The survey of upland backslope soils included north- and south-facing hillslopes derived from three lithologies (slate, metavolcanic, and phyllite). The soils across all sites were very gravelly (51.8 ± 20.4% coarse fragments), acidic (mineral soil pH 4.85 ± 0.45), and moderately deep (96.56 ± 37.80 cm); thin, broken E horizons were underlain by thick, carbon-rich spodic horizons. Soil development was relatively consistent as demonstrated by the Profile Development Index with values from 15 to 26 and Podzolization Index values spanning 8 to 14. A mean pedon SOC stock of 198.02 ± 81.42 Mg C ha−1 (n = 18) was calculated using data collected for all upland organic and mineral soils from our work. The accumulation of SOC was similar among soils formed from contrasting lithologies with averages of 182 ± 15.70 Mg C ha−1 for slate, 188 ± 53.80 Mg C ha−1 for metavolcanic, and 218 ± 124 Mg C ha−1 for phyllite. Our work contributes to soil morphological observations, laboratory data, and SOC stock estimates required to better constrain and model pedogenic processes and SOC stock in remote forests where data sets are limited. [ABSTRACT FROM AUTHOR]

Quantifying soil redistribution rates, including both erosion and deposition, is critical for understanding erosion processes, landscape evolution, land management strategies, and the carbon cycle. In the Northeast Pacific coastal temperate rainforest, the interaction of perhumid climate and dense coniferous forest tends to form Spodosols which are soils characterized by a subsurface accumulation of organic matter and iron and aluminum oxides, across a range of contrasting lithologies. Deep Spodosols are frequently found on steep backslopes (up to 60%) of colluvial deposits, where shallower soils would typically be expected. We hypothesized that deep Spodosols in Southeast Alaska indicate slope stability, exhibiting negligible soil redistribution rates and stable surfaces regardless of the lithology. Our objective was to quantify soil redistribution rates for Spodosols formed on steep slopes across a range of lithologies in hilly and mountainous areas of Juneau, AK. We used 239+240Pu isotopes to quantify soil erosion and deposition rates in Spodosols formed on colluvial deposits from tonalite, slate, metavolcanic rock, and phyllite. 239+240Pu measurements revealed negligible soil redistribution rates for all studied pedons, ranging from erosion rates of 0.51 t/ha/year to deposition rates up to 0.43 t/ha/year. No difference was detected between the hill and mountain landforms, further supporting the idea that Spodosols could indicate slope stability over decadal timescales across the region. Understanding the resilience of Spodosols to erosion processes in varied lithologies and landforms on steep slopes is paramount for making informed decisions regarding sustainable land use, landslide risk mitigation, and effective carbon sequestration strategies. [ABSTRACT FROM AUTHOR]

Amidst the backdrop of contemporary conflicts and hostilities unfolding across various regions globally, the landscape of higher education is confronted with a myriad of novel challenges and prospects. War initiates the need for rapid and effective innovations in education to ensure access to learning in times of crisis. The objective of this article is to assess and scrutinize the application of modern technologies in higher education amid periods of conflict, focusing specifically on their influence on educational accessibility and quality within nations grappling with wartime circumstances. To achieve this goal, an analysis of scientific literature and publications was conducted. The conducted research revealed that the utilization of modern technologies in higher education during the war contributes to increasing the availability and quality of education. These technologies make it possible to provide distance learning using remote forms of communication and learning. The conclusions show, that the utilization of modern technologies in education is a key factor in ensuring continuous learning during war and conflict. These technologies allow efficient use of resources and provide a high-quality educational environment for students in difficult conditions. [ABSTRACT FROM AUTHOR]

It was found that the modification of commercial activated carbon grades F400 and AS-CS with ferric oxide obtained from alumina production waste "red mud" allows increasing the sorption capacity of activated carbon grade F400 to 60.241 mg/g (2 times). At the same time, the maximum sorption capacity of activated carbon AS-CS increases almost 7 times. The content of Fe2O3 fixed in the structure of activated carbon reaches 9.14%. It has been established that the modification forms an additional number of phenolic groups on the surface of the material, which contributes to an increase in the anion exchange capacity of the sorption material by 2.55 times. The sorption material is effective for removing phosphorus compounds from water at the level of 88.1% and can be recommended for use in the treatment of industrial water. [ABSTRACT FROM AUTHOR]