Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group.

Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs\u27 therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy

Optimized bioethanol production from Lemna minuta biomass harvested from polluted water via acid and enzymatic hydrolysis.

ABSTRACT: The contamination of water bodies through domestic, agricultural, and industrial discharges remains a critical environmental challenge, leading to eutrophication and harmful impacts on aquatic ecosystems and public health. In response, phytoremediation, which utilizes aquatic plants for pollutant removal, have gained attention. This study investigates the potential of Lemna minuta biomass, harvested from a polluted pond, for bioethanol production. The research evaluates carbohydrate content and explores the efficiency of acid and enzymatic hydrolysis in converting the biomass into fermentable sugars. The study’s findings reveal that Lemna minuta exhibits a carbohydrate content of 36.46 ± 1.69%. Acid hydrolysis demonstrated a high conversion efficiency, with optimal conditions achieving up to 99.20% efficiency and 18.09 g L−1 total reducing sugars. Enzymatic hydrolysis, while effective, yielded lower efficiencies, indicating the need for further optimization. Fermentation tests using Saccharomyces cerevisiae chardonnay resulted in ethanol production of 1.5 g L−1 , highlighting the potential of Lemna minuta as a sustainable bioethanol feedstock. These findings highlight the potential of Lemna minuta as a sustainable feedstock for bioethanol production while contributing to environmental remediation, reinforcing its dual role in renewable energy and ecosystem restoration

Eco-efficiency assessment and food security potential of home gardening: a case study in Padua, Italy

In the expanding urban agriculture phenomenon in Europe, home gardens are a traditional form that have kept agriculture within cities, even becoming crucial in certain historical periods (e.g., war periods). However, horticultural practices in home gardens can also have negative consequences. The goal of this paper is to assess the eco-efficiency of home gardens as a type of urban agriculture. To do so, a case study in Padua (Italy) was evaluated following life cycle assessment and life cycle costing methods. A home garden of 30.6 m(2) and 21 crop cycles were evaluated. The functional unit of the assessment was 1 kg of harvested fresh vegetable at the consumption point, and the ReCiPe method was employed for impact assessment. Environmental assessment indicated that organic fertilization, use of tap water, mineral fertilization and pesticides were the most contributing elements of the entire life cycle. Furthermore, the relevance of garden design and crop selection was a determinant in the eco-efficiency results. The assessed home garden could satisfy the food requirements of between 1 and 2 members of the household. Crop management and design recommendations are provided to improve eco-efficiency and food security potential of home gardens

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Activity in Inferior Parietal and Medial Prefrontal Cortex Signals the Accumulation of Evidence in a Probability Learning Task

In an uncertain environment, probabilities are key to predicting future events and making adaptive choices. However, little is known about how humans learn such probabilities and where and how they are encoded in the brain, especially when they concern more than two outcomes. During functional magnetic resonance imaging (fMRI), young adults learned the probabilities of uncertain stimuli through repetitive sampling. Stimuli represented payoffs and participants had to predict their occurrence to maximize their earnings. Choices indicated loss and risk aversion but unbiased estimation of probabilities. BOLD response in medial prefrontal cortex and angular gyri increased linearly with the probability of the currently observed stimulus, untainted by its value. Connectivity analyses during rest and task revealed that these regions belonged to the default mode network. The activation of past outcomes in memory is evoked as a possible mechanism to explain the engagement of the default mode network in probability learning. A BOLD response relating to value was detected only at decision time, mainly in striatum. It is concluded that activity in inferior parietal and medial prefrontal cortex reflects the amount of evidence accumulated in favor of competing and uncertain outcomes

Processing Eucalyptus cloeziana seed lots to improve purity, germination and vigor.

Eucalyptus cloeziana is one of the highest-density wood species offering significant added value, frequently used in the construction and furniture industries. Despite its suitability, it may be overlooked on account of its propagation difficulties due either to its low rooting cutting capacity or to its seeds having a low germination rate perhaps attributable to the high proportion of indistinguishable impurities within the seed lots. This study aimed to develop an efficient technique for Eucalyptus cloeziana seed processing to increase the physical purity and, consequently, the physiological quality of the seed lot. Three seed lots, separated by size in sieves with 1.18, 1.00, and 0.84 mm square openings, were used. X-ray analyses were carried out, the number of normal seedlings and germination rate identified and the percentage and speed of seedling emergence under greenhouse conditions ascertained. The greenhouse evaluation showed that the seed retained in the 1.18 mm sieve presented viability and vigor twice that of the control. Therefore, the processing technique by size classification is efficient in terms of improving the physical and physiological performance of Eucalyptus cloeziana seed lots

Phycoremediation of ten sulfonamide antibiotics in swine wastewater: Microalgal tolerance, toxicity, and carbohydrate-rich biomass production.

This study investigates the removal of ten sulfonamide antibiotic residues from swine wastewater using Chlorella spp. in a phycoremediation process. The effects of sulfonamides on microalgal biomass production, pigment content (chlorophyll α, chlorophyll b, and carotenoids), and the genotoxicity of treated water were evaluated. Sulfonamides were tested at concentrations of 0.1, 1.0, 10, 50, and/or 100 mg L⁻¹ , with the antibiotic removal specifically assessed at 10 mg L⁻¹ . Results showed that Chlorella spp. exhibited robust biomass growth and maintained stable pigment production, even at the highest concentrations, indicating the microalgae's tolerance to antibiotic exposure. The removal efficiency for sulfonamides was notably high, particularly for sulfamethoxazole (70 %), sulfachlorpyridazine (55 %), and sulfamerazine and sulfamethizole (50 %) at the 10 mg L⁻¹ concentration. Genotoxicity assays with Allium cepa revealed minimal chromosomal aberrations, suggesting that the treated wastewater posed a low genotoxic risk. The microalgal biomass, characterized by high carbohydrate content, also holds promise for biofuel production. These findings highlight Chlorella spp. as an effective and sustainable solution for mitigating antibiotic pollution in agricultural wastewater, while simultaneously providing valuable biomass for renewable energy applications