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Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed (R/R) B-cell non-Hodgkin lymphoma (NHL). Several risk factors including CAR-T cell-related toxicities and their treatments often lead to infectious complications (ICs); however, the pattern and timeline is not well established. We evaluated ICs in 48 patients with R/R B-cell NHL following CAR-T cell therapy at our institution. Overall, 15 patients experienced 22 infection events. Eight infections (4 bacterial, 3 viral and 1 fungal) occurred within the first 30 days and 14 infections (7 bacterial, 6 viral, 1 fungal) between days 31 to 180 following CAR-T infusion. Most infections were mild-to-moderate and fifteen infections involved the respiratory tract. Two patients developed mild-to-moderate COVID-19 infection and one patient a cytomegalovirus reactivation after CAR-T infusion. Two patients developed IFIs: one case each of fatal disseminated candidiasis and invasive pulmonary aspergillosis at day 16 and 77, respectively. Patients with more than 4 prior antitumor regimens and patient's ≥ 65 years had a higher infection rate. Infections in patients with relapsed/refractory B-cell NHL are common after CAR-T despite the use of infection prophylaxis. Age ≥ 65 years and having > 4 prior antitumor treatments were identified as risk factors for infection. Fungal infections carried significant impact in morbidity and mortality, suggesting a role for increase fungal surveillance and/or anti-mold prophylaxis following high-dose steroids and tocilizumab. Four of ten patients developed an antibody response following two doses of SARS-CoV-2 mRNA vaccine. [ABSTRACT FROM AUTHOR]

We develop an explicit algebraic Reynolds stress model (EARSM) for high-speed compressible shear flows and validate the model with direct numerical simulation (DNS) data of homogeneous shear flow and experimental data of high-speed mixing-layers. Starting from a pressure-strain correlation model that incorporates compressibility effects, the weak-equilibrium assumption is invoked to derive the EARSM closure expression. The resulting closure is fully explicit and physically realizable and is a function of mean flow strain rate, rotation rate, turbulent kinetic energy, dissipation rate, and gradient Mach number. Homogeneous shear flow calculations show that the model captures the asymptotic behavior of DNS quite well. Linear EARSM calculations of a plane supersonic mixing-layer are performed, and comparison with experimental data shows good agreement. Salient results are agreement of streamwise velocity similarity profiles, mixing-layer spreading rates, and capturing the Langley curve trend. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Brushing, the standard sampling method at endoscopic retrograde cholangiography (ERC), lacks sensitivity for cancer detection. We assessed a novel sampling method using a grasping basket. METHODS: Fifty-six patients with a suspected malignant biliary stricture were randomized to biliary sampling at ERC using a basket (basket group, N = 30) or a brush (brush group, N = 26), followed by the alternate device. When deemed necessary, strictures were dilated (using 6-mm balloons exclusively). The primary end point was sensitivity for cancer detection at cytopathological examination of the first sample collected in each patient; the cytopathologist was blinded to clinical details and sampling method. All analyses followed an intention-to-treat principle. RESULTS: All 56 patients had successful sampling with both techniques; 50 (89%) had a final diagnosis of malignant stricture. Sensitivity for cancer detection with the first sample collected in each patient was significantly higher in the basket compared to brush group (20/25 [80%] vs 12/25 [48%], respectively, P= 0.018, OR 4.33, 95% CI 1.24–15.21). Seventeen (34%) of the 50 sample pairs collected from malignant cases showed discordant cytopathological results: 15 patients had a positive basket and a negative brush result while two had the inverse association ( P= 0.002, OR 7.5, 95% CI 1.65–47.44). Basketting more frequently yielded positive samples from malignant strictures in case of presampling balloon dilation (27/32 [84%] vs 10/18 [56%], respectively, P= 0.043, OR 4.32, 95% CI 1.14–16.37). Specificity was 100% (both methods). CONCLUSION: Biliary sampling at ERC using a dedicated basket provided a significantly higher sensitivity for cancer detection than brushing; presampling stricture dilation significantly increased sensitivity. [ABSTRACT FROM AUTHOR]

The tubby mouse, which shows late-onset obesity and neurosensory deficits, arises from a mutation in the Tub gene. Tub shares homology with the genes for tubby-like proteins Tulp1, Tulp2 and Tulp3. Ablation of Tub, Tulp1 or Tulp3 causes disease phenotypes that are indicative of their importance in nervous-system function and development. Despite this importance, the biochemical functions of tubby-like proteins are only now beginning to be understood. At present, data indicate that tubby-like proteins might function as heterotrimeric-G-protein-responsive intracellular signalling factors, although an array of data also implicates them in other processes. [ABSTRACT FROM AUTHOR]

Proposes a mathematical model based on the competition between neural networks. Competition between the neural network controlling lever-pressing response during variable-interval schedules of reinforcement with other behavior-controlling networks; Expression of the behavior by a winner-take-all mechanism.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]