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PurposeChimeric antigen receptor (CAR) T-cell CD19 therapy has changed the treatment paradigm for patients with relapsed/refractory B-cell acute lymphoblastic leukemia. It is frequently associated with potentially severe toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and admission to PICU is often required. Some biomarkers seem to correlate with CRS severity. Our goal is to elucidate the role of procalcitonin (PCT), C-reactive protein (CRP) and ferritin in the context of CRS following CAR T-cell infusion to predict its severity and PICU admission.MethodsProspective observational study (2016-2022) in children and young adult who received CAR T-cell therapy (Tisagenlecleucel/ARI-0001). We collected epidemiologic data, specific CAR T-cell toxicities, PICU admission, biomarker results (procalcitonin, CRP and ferritin), length of stay and mortality. Biomarkers were analyzed considering two values: the highest value during ward admission, and the highest overall value including PICU admission.ResultsSeventy-seven patients were included. Median age at infusion was 9.1 years (IQR 6-13), 49.4% were females. Before CAR T-cell infusion, the median bone marrow blast was 9% (IQR 0-59). The most frequent toxicity was CRS in 62 patients (80.5%), it was severe in 18 cases (23.4%). Fourteen patients (18.1%) had ICANS. Thirty-one patients (40.3%) required admission to the PICU. PCT and ferritin were higher in patients admitted to PICU (PCT 0.8 ng/ml vs 0.15 ng/ml, p < 0.001, ferritin 5490 vs. 2900 ug/l, p < 0.019). The proposed cut-off for PCT to predict admission to PICU is 0.55 ng/mL, presenting a sensitivity of 67.7% and a specificity of 86.7%. The maximum value of the three biomarkers was higher in those who presented any primary outcome: development of a severe CRS, the need for admission to PICU, and in-hospital mortality. Biomarkers were higher in those who needed inotropic or respiratory support.ConclusionsPCT levels increase after CAR-T cell therapy in the setting of systemic inflammation and could be a predictor of PICU admission and evolution to death. Further research studying its role in the context of CRS and the differential diagnosis between infection and CRS is needed to better understand the biology of this biomarker and to define its value in clinical practice.

Federated learning (FL) allows model training from local data collected by edge/mobile devices while preserving data privacy, which has wide applicability to image and vision applications. A challenge is that client devices in FL usually have much more limited computation and communication resources compared to servers in a data center. To overcome this challenge, we propose PruneFL -a novel FL approach with adaptive and distributed parameter pruning, which adapts the model size during FL to reduce both communication and computation overhead and minimize the overall training time, while maintaining a similar accuracy as the original model. PruneFL includes initial pruning at a selected client and further pruning as part of the FL process. The model size is adapted during this process, which includes maximizing the approximate empirical risk reduction divided by the time of one FL round. Our experiments with various datasets on edge devices (e.g., Raspberry Pi) show that: 1) we significantly reduce the training time compared to conventional FL and various other pruning-based methods and 2) the pruned model with automatically determined size converges to an accuracy that is very similar to the original model, and it is also a lottery ticket of the original model.

The unique diffraction geometry of ESRF beamline ID06-LVP offers continuous static 2D or azimuthally resolving data collections over all accessible solid angles available to the tooling geometry. The system is built around a rotating custom-built Pilatus3 CdTe 900k-W detector from Dectris, in a configuration equivalent to three butted 300k devices. As a non-standard geometry, here the method of alignment, correction and subsequent integration for any data collected over all solid angles accessible, or over any azimuthal range contained therein, are provided and illustrated by parameterizing and extending existing pyFAI routines. At 1° integrated intervals, and typical distances (2.0 m), the system covers an area of near 2.5 m 2 (100 Mpx square equivalent), to 0.65 Å resolution, at 53 keV from a total dataset of some 312 Mpx. Standard FWHMs of SRM660a LaB 6 vary from 0.005° to 0.01°, depending on beam size, energy and sample dimensions, and are sampled at an elevated rate. The azimuthal range per static frame ranges from <20° to ∼1° over the full range of the detector surface. A full 2θ-intensity data collection at static azimuth takes 1-3 s typically, and can be reduced to ms -1 rates for measurements requiring time-rate determination. A full solid-angle collection can be completed in a minute. Sample detector distances are accessible from 1.6 m to 4.0 m., (open access.)

Background: We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19., Methods: We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias., Results: Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67-1.07; P = 0.16; I 2  = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73-1.08; P = 0.24; I 2 : 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28-0.62; P = 0.0001; I 2  = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]., Conclusion: Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction. The degree of Dornic acidity (DA) is an indirect measure of milk contamination and quality. In freshly expressed milk, DA ranges between 1.0 and 4.0 (optimal). If DA is > 8.0 °D, it should be discarded. The correlation between DA in raw breast milk from internal donors (ID) and external donors (ED) based on storage time until pasteurization was assessed. Population and method. Retrospective, analytical study. Results. In 13 203 samples, DA was lower in IDs as of 14 days of storage: 2.92 (95% CI: 2.69-3.15) versus 4.01 (95% CI: 3.94-4.08), with a higher proportion of DA ≤ 4 °D (88% in IDs versus 76% in EDs); odds ratio: 2.30 (95% CI: 1.25-4.24). Conclusion. DA as of 14 days of storage was lower in IDs, with a higher prevalence of DA ≤ 4 °D. No correlation was observed between storage time and DA in ID samples., (Sociedad Argentina de Pediatria.)

Background: Recent studies have shown the presence of SARS-CoV-2-specific antibodies in the milk of breastfeeding mothers vaccinated with mRNA and convalescent. However, limited information is available in lactating women receiving other vaccine platforms used in developing countries, such as the inactivated SARS-CoV-2 vaccine BBIBP-CorV (Sinopharm) and the non-replicating adenovirus vaccines Sputnik V (Gamaleya Institute) and ChAdOx1-S (Oxford AstraZeneca)., Methods: Here, we evaluated anti-SARS-CoV-2 IgG and IgA levels in both serum and milk samples using a longitudinal and a cross-sectional cohort of 208 breastfeeding vaccinated women from Argentina with or without previous SARS-CoV-2 infection., Results: The analysis showed that IgA levels remain constant in serum and milk of breastfeeding mothers between the first and second doses of vector-based vaccines (Sputnik V and ChAdOx1-S). After the second dose, anti-spike IgA was found positive in 100% of the serum samples and in 66% of breastmilk samples. In addition, no significant differences in milk IgA levels were observed in participants receiving BBIBP-CorV, Sputnik V or ChAdOx1-S. IgG levels in milk increased after the second dose of vector-based vaccines. Paired longitudinal samples taken at 45 and 120 days after the second dose showed a decrease in milk IgG levels over time. Study of IgA levels in serum and milk of vaccinated naïve of infection and vaccinated-convalescent breastfeeding participants showed significantly higher levels in vaccinated-convalescent than in participants without previous infection., Conclusion: This study is relevant to understand the protection against SARS-CoV-2 by passive immunity in newborns and children who are not yet eligible to receive vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Longueira, Ojeda, Battistelli, Sanchez, Oviedo Rouco, Albano, Guevara, Valls, Pando and Gamarnik.)

An effective warning attracts attention, elicits knowledge, and enables compliance behavior. Game mechanics, which are directly linked to human desires, stand out as training, evaluation, and improvement tools. Immersive virtual reality (VR) facilitates training without risk to participants, evaluates the impact of an incorrect action/decision, and creates a smart training environment. The present study analyzes the user experience in a gamified virtual environment of risks using the HTC Vive head-mounted display. The game was developed in the Unreal game engine and consisted of a walk-through maze composed of evident dangers and different signaling variables while user action data were recorded. To demonstrate which aspects provide better interaction, experience, perception and memory, three different warning configurations (dynamic, static and smart) and two different levels of danger (low and high) were presented. To properly assess the impact of the experience, we conducted a survey about personality and knowledge before and after using the game. We proceeded with the qualitative approach by using questions in a bipolar laddering assessment that was compared with the recorded data during the game. The findings indicate that when users are engaged in VR, they tend to test the consequences of their actions rather than maintaining safety. The results also reveal that textual signal variables are not accessed when users are faced with the stress factor of time. Progress is needed in implementing new technologies for warnings and advance notifications to improve the evaluation of human behavior in virtual environments of high-risk surroundings.

The creation and usage of serious games on virtual reality (VR) and/or interactive platforms for the teaching of architecture, construction, urban planning, and other derived areas, such as security and risk prevention, require design processes, studies, and research that lead to further consolidation expansion. In that sense, this paper presents two main aims developed: the improvement of a virtual navigation system through the results of previous user studies and mixed research (quantitative and qualitative) improved based on the user perception for educational and professional uses. The VR system used is based on Unreal Engine programming of the HTC Vive sensor. This study is related to the GAME4City 3.0 and a broader project focused on gamified visualization and its educational uses in architectural and urban projects. The results reflect great interest, good usability, and high motivation for further usage for all types of users. However, an apparent resistance to deepen its use continues to be perceived in academia. Based on the research results, weak points of educational gamified systems have been identified, and the main differences and needs in user profiles' function. With these data, progress regarding implementing this kind of system at the teaching and professional levels must be pursued.

Background: Ethanol (EtOH), one of the most widely consumed substances of abuse, can induce brain damage and neurodegeneration. EtOH is centrally metabolized into acetaldehyde, which has been shown to be responsible for some of the neurophysiological and cellular effects of EtOH. Although some of the consequences of chronic EtOH administration on cell oxidative status have been described, the mechanisms by which acute EtOH administration affects the brain's cellular oxidative status and the role of acetaldehyde remain to be elucidated in detail., Methods: Swiss CD-I mice were pretreated with the acetaldehyde-sequestering agent d-penicillamine (DP; 75 mg/kg, i.p.) or the antioxidant lipoic acid (LA; 50 mg/kg, i.p.) 30 minutes before EtOH (2.5 g/kg, i.p.) administration. Animals were sacrificed 30 minutes after EtOH injection. Glutathione peroxidase (GPx) mRNA levels; GPx and glutathione reductase (GR) enzymatic activities; reduced glutathione (GSH), glutathione disulfide (GSSG), glutamate, g-L-glutamyl-L-cysteine (Glut-Cys), and malondialdehyde (MDA) concentrations; and protein carbonyl group (CG) content were determined in whole-brain samples., Results: Acute EtOH administration enhanced GPx activity and the GSH/GSSG ratio, while it decreased GR activity and GSSG concentration. Pretreatment with DP or LA only prevented GPx activity changes induced by EtOH., Conclusions: Altogether, these results show the capacity of a single dose of EtOH to unbalance cellular oxidative homeostasis., (© 2019 by the Research Society on Alcoholism.)

Within the framework of the ESRF Phase I Upgrade Programme, a new state-of-the-art synchrotron beamline ID16B has been recently developed for hard X-ray nano-analysis. The construction of ID16B was driven by research areas with major scientific and societal impact such as nanotechnology, earth and environmental sciences, and bio-medical research. Based on a canted undulator source, this long beamline provides hard X-ray nanobeams optimized mainly for spectroscopic applications, including the combination of X-ray fluorescence, X-ray diffraction, X-ray excited optical luminescence, X-ray absorption spectroscopy and 2D/3D X-ray imaging techniques. Its end-station re-uses part of the apparatus of the earlier ID22 beamline, while improving and enlarging the spectroscopic capabilities: for example, the experimental arrangement offers improved lateral spatial resolution (∼50 nm), a larger and more flexible capability for in situ experiments, and monochromatic nanobeams tunable over a wider energy range which now includes the hard X-ray regime (5-70 keV). This paper describes the characteristics of this new facility, short-term technical developments and the first scientific results.