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Abstract Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets ( 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial to better guide individualized management of high-risk patients, but specific predictive markers are still missing. Serum neurofilament light chain (NfL) levels are a sensitive indicator of neuroaxonal injury in neurological diseases. Elevated NfL levels at the time of CAR T-cell infusion have been associated with the severity of ICANS, but their utility for earlier identification of patients with subclinical neurological damage has not been evaluated.We studied all consecutive adult patients who received commercial CAR T cells for relapsed/refractory B-cell lymphomas at Saint-Louis Hospital between January 2019 and February 2023. Patients with pre-existing or current neurological disease were excluded. NfL levels were quantified in frozen serum collected at the time of the decision to treat (ie, the day of leukapheresis) and at the time of treatment (ie, the day of infusion).Of the 150 study patients, 28% developed ICANS of any grade, including 15.3% of grade 2–4. Receiving a CAR construct with a CD28 domain (58% of patients) was the strongest predictor of grade 2–4 ICANS. Serum NfL levels were significantly higher in patients with grade 2–4 ICANS than in those with grade 0–1 ICANS, both at the time of leukapheresis and infusion. In multivariate models, NfL above the cut-off value was independently associated with grade 2–4 ICANS at leukapheresis (NfL>75 pg/mL, OR 4.2, 95% CI 1.2 to 14.2, p=0.022) and infusion (NfL>58 pg/mL, OR 4.3, 95% CI 1.3 to 13.7, p=0.015).In conclusion, high NfL levels at the time of the decision to proceed with CAR T-cell manufacturing may represent an early surrogate of underlying loss of neuroaxonal integrity that increases the risk of subsequent neurotoxicity. Incorporating NfL levels into the decision-making process based on each patient’s risk profile could help determine the appropriate CAR product when possible, and guide the prophylactic or therapeutic management of ICANS.

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The Study Demands and Resources Scale (SDRS) has shown promise as a valid and reliable measure for measuring students’ specific study demands and -resources. However, there is no evidence as to its psychometric properties outside of the original context in which it was developed. This study aimed to assess the psychometric properties of the SDRS in a cross-national student population through examining its longitudinal factorial validity, internal consistency, and temporal invariance as well as criterion validity through its association with study engagement and task performance over time. Results showed that a Bifactor Exploratory Structural Equation Model (ESEM) with one general factor (overall study characteristics) and five specific factors (workload, growth opportunities, lecturer support, peer support, information availability) fitted the data, showed strong measurement invariance over time, and was reliable at different time points. The study further established criterion validity for the overall study characteristics factor through its concurrent and predictive associations with study engagement and task performance. However, the specific factors’ concurrent and predictive capacity could only partially be established when controlling for the general study characteristics factor. These findings suggest that study characteristics should be measured as a dynamic interaction between study demands and resources, rather than a hierarchical model.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Abstract Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here, we report the development of a high throughput non-invasive method for tracking mammalian cell growth and performance based on plate reader measurements. We show the method to be suitable for both suspension and adhesion cell lines, and we demonstrate it can be adopted when cells are grown under different environmental conditions. We establish that the method is suitable to inform on effective drug treatments to be used depending on the cell line considered, and that it can support characterisation of engineered mammalian cells over time. This work provides the scientific community with an innovative approach to mammalian cell screening, also contributing to the current efforts towards high throughput and automated mammalian cell engineering.

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement.

The benefits deriving from the coexistence of energy production from a photovoltaic plant and crops growth on the same land have been investigated in Enel Green Power photovoltaic plant of Totana, in the semi-arid region of Murcia, in Spain. In this area, scarcity of water resources and high temperatures can have a major impact on production and agrivoltaic can be relevant for the potential benefits of shading on crops. Pepper “Bola”, aloe vera and thyme have been selected for their economic importance and adaptation to the conditions of the area. The results reported are related to the testing areas in the corridors between two modules rows and to the control area. For pepper, an increase of more than 60% in the agricultural yield and in fresh mean weight and of more than 30% for the fruits number have been observed in the corridors, with respect to the control area. For aloe and thyme in the corridor zone a higher plant biomass (more than 30% and 20%, respectively) has been recorded, compared to the control area. An increase of 11% in weight of the fresh biomass has also been detected for thyme in the corridor after about one year from the implementation. The results obtained in the first year have shown that the intermittent shade and microclimate generated by the photovoltaic panels in the corridor area could benefit pepper, aloe vera and thyme cultivation. These trials will continue in next crop cycles, to confirm the preliminary results.

The Channichthyidae, a monophyletic fish group belonging to the suborder Notothenioidei, are uniquely adapted to the polar environment. However, while their physiology has been extensively studied, studies on their ecology are relatively rare. Here, we investigated the trophic ecology of seven icefish species (Chaenodraco wilsoni, Chionobathyscus dewitti, Chionodraco hamatus, Dacodraco hunteri, Neopagetopis ionah, Pagetodes antarcticus and Pagetopsis macropterus) by using the traditional morphometric approach to assess the relationship between form and feeding function. The suction index (SI), the mechanical advantage in jaw closing (MA) and nine morphological traits related to feeding structures have been analysed. Icefish species are characterised by non-protractible, elongate jaws and a wide gape; such morphological features influence the low values of both MA and SI, supporting their ram-feeding habit. The ecomorphological differences among species resulted mainly determined by the anatomical structures related to SI. Such differences do not seem to be determined primarily by the type of prey, as is the case in other taxonomic groups of Notothenioidei, but rather by phylogenetic proximity. A 3D animation was developed to visualise the different feeding modes of two icefish species (C. hamatus and P. macropterus) which are characterised by different approaches to prey.

PurposeSavouring interventions aim to amplify the intensity and duration of positive feelings and positive affect. Research has shown that the potential benefits of savouring include the promotion of psychological well-being and diminution of negative affective states. Savouring strategies may be particularly useful amongst clinical populations in changing biobehavioural processes which can strengthen an individual's propensity to exert control over how to develop, intensify and promote psychological well-being, while simultaneously mitigating negative affective states. This paper outlines a protocol for a systematic review that will be used to identify, critically appraise and synthesise findings of studies examining the effectiveness of savouring interventions in adult clinical populations. Savouring interventions will be defined broadly, operationalised as any savouring strategy focusing on past, present or future events or experiences whereby participants are instructed to attend to and amplify positive affect relating to same. The goal of our review is to include the extent of the literature on this topic and contribute to the overall evidence to support savouring interventions.MethodsThis protocol is carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols Guidelines. The protocol has been registered with PROSPERO (CRD42023404857). The databases PsycINFO, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Scopus will be searched alongside a search of grey literature. An examination of the first 200 papers on Google Scholar will also be done to identify relevant papers. Studies describing randomised controlled trials evaluating the effects of savouring interventions as described within this article on adult clinical populations will be included in the review. Outcomes will include well-being, quality of life, depression, anxiety or stress. Study selection and data extraction will be completed by three independent reviewers to reduce risk of bias. Interrater percentage agreement and interrater reliability will be reported on same. The quality of studies will be assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias and the Jadad scale. A narrative synthesis with tables of study characteristics will be provided. Separate considerations of the three time perspectives of savouring interventions (past-focused, present-focused, and future-focused) will also be described.ConclusionsThis systematic review will provide important clinical insights into the potential efficacy of savouring interventions when working with adult clinical samples.

BackgroundPoor employee mental health and wellbeing are highly prevalent and costly. Time-related factors such as work intensification and perceptions of time poverty or pressure pose risks to employee health and wellbeing. While reviews suggest that there are positive associations between time management behavior and wellbeing, there is limited rigorous and systematic research examining the effectiveness of time management interventions on wellbeing in the workplace. A thorough review is needed to synthesize time management interventions and their effectiveness to promote employee mental health and wellbeing.MethodA systematic search will be conducted using the following databases: PsychINFO via OVID (1806-Present), Web of Science, Scopus via Elsevier (1976-Present), Academic Search Complete (EBSCO), Cochrane Library via Wiley (1992-Present), and MEDLINE via OVID (1946-Present). The review will include experimental and quasi-experimental studies that evaluate the effects of time management interventions on wellbeing outcomes on healthy adults in a workplace context. Only studies in English will be included. Two authors will independently perform the literature search, record screening, data extraction, and quality assessment of each study included in the systematic review and meta-analysis. Data will be critically appraised using the Cochrane risk-of-bias tools. Depending on the data, a meta-analysis or a narrative synthesis will be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in the development of this protocol. The protocol has been registered in PROSPERO (CRD4202125715).DiscussionThis review will provide systematic evidence on the effects of time management interventions on wellbeing outcomes in the workplace. It will contribute to our understanding of how time management approaches may help to address growing concerns for employee mental health and wellbeing.

The effects of the co-location of energy production from a photovoltaic (PV) plant and aromatic crops (thyme, oregano, and Greek mountain tea) in a hot and dry environment have been investigated in Enel Green Power PV plant located in Kourtesi (Greece). The study was aimed at evaluating the influence of the PV plant on microclimate, on soil temperature and water potential, and on the crops’ growth in a testing area (the corridors between two modules rows) compared to a full sunlight control area. The net radiation and of the wind speed recorded in the testing area showed a 44% and 38% reduction respectively, compared to the control area, while air temperature and relative humidity did not show any difference. Among crop/soil monitored parameters, cumulative reference evapotranspiration (ET0) and the average soil temperature were found 29% and 8% lower in the testing area, conversely the soil water potential (SWP) was 34% higher compared to control area. No significant differences in the plant growth have been detected between testing and control areas, except for oregano whose weight was higher in testing area. The results suggest that in hot and dry climatic conditions, the reduction of climatic stress could compensate the decrease of photosynthesis due to the shading effect of the PV modules, thus not damaging crops’ growth.

Recurrent gene fusions (GFs) in translocated sarcomas are recognized as major oncogenic drivers of the disease, as well as diagnostic markers whose identification is necessary for differential diagnosis. EWSR1 is a ‘promiscuous’ gene that can fuse with many different partner genes, defining different entities among a broad range of mesenchymal neoplasms. Molecular testing of EWSR1 translocation traditionally relies on FISH assays with break-apart probes, which are unable to identify the fusion partner. Therefore, other ancillary molecular diagnostic modalities are being increasingly adopted for accurate classification of these neoplasms. Herein, we report three cases with rare GFs involving EWSR1 in undifferentiated mesenchymal neoplasms with uncertain differential diagnoses, using targeted RNA-seq and confirming with RT-PCR and Sanger sequencing. Two GFs involved hormone nuclear receptors as 3′ partners, NR4A2 and RORB, which have not been previously reported. NR4A2 may functionally replace NR4A3, the usual 3′ partner in extraskeletal myxoid chondrosarcoma. The third GF, EWSR1::BEND2, has previously been reported in a subtype of astroblastoma and other rare entities, including a single case of a soft-tissue tumor that we discuss in this work. In conclusion, our findings indicate that the catalogue of mesenchymal neoplasm-bearing EWSR1 fusions continues to grow, underscoring the value of using molecular ancillary techniques with higher diagnostic abilities in the routine clinical setting.

This paper presents a code-to-code verification of the SPERT-III reactor in its E-core configuration using the Monte Carlo codes TRIPOLI-4®, TRIPOLI-5® and OpenMC. A SPERT-III E-core model was originally developed for the Monte Carlo code TRIPOLI-4® and will be the baseline of our analysis The simulation results obtained for the main reactor physics parameters (neutron effective multiplication factor, rod worth, reactivity coefficients and kinetics parameters) with TRIPOLI-4®and OpenMC using different nuclear data libraries are compared and analyzed. Additional verifications are carried out with the next-generation Monte Carlo code TRIPOLI-5®, which is currently under development by CEA and IRSN (France). This paper summarizes a joint study that was conducted within an international research collaboration between CEA Paris-Saclay (France) and the Nuclear Research Center Negev (NRCN, Israel), and is a stepping stone towards future multi-physics simulations exploring the SPERT-III reactor power excursions, including thermal-hydraulics feedback.

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement. [ABSTRACT FROM AUTHOR]

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel. [ABSTRACT FROM AUTHOR]