Interpretable Machine Learning Models for Practical Antimonate Electrocatalyst Performance.

Computationally predicting the performance of catalysts under reaction conditions is a challenging task due to the complexity of catalytic surfaces and their evolution in situ, different reaction paths, and the presence of solid-liquid interfaces in the case of electrochemistry. We demonstrate here how relatively simple machine learning models can be found that enable prediction of experimentally observed onset potentials. Inputs to our model are comprised of data from the oxygen reduction reaction on non-precious transition-metal antimony oxide nanoparticulate catalysts with a combination of experimental conditions and computationally affordable bulk atomic and electronic structural descriptors from density functional theory simulations. From human-interpretable genetic programming models, we identify key experimental descriptors and key supplemental bulk electronic and atomic structural descriptors that govern trends in onset potentials for these oxides and deduce how these descriptors should be tuned to increase onset potentials. We finally validate these machine learning predictions by experimentally confirming that scandium as a dopant in nickel antimony oxide leads to a desired onset potential increase. Macroscopic experimental factors are found to be crucially important descriptors to be considered for models of catalytic performance, highlighting the important role machine learning can play here even in the presence of small datasets.

Efficacy and safety of MAS825 (anti-IL-1ß/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function.

MAS825, a bispecific IL-1ß/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1ß and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.

Pre-migration trauma and HIV-risk behavior.

This study examined the relationship between pre-migration trauma and HIV-risk behavior in refugees from sub-Saharan Africa. The sample comprised 122 persons who had emigrated from sub-Saharan Africa and were currently residing in Sweden. Qualitative methods including individual interviews, focus groups, and interviews with key informants addressed questions regarding trauma experience and HIV-risk behavior. A history of pre-migration trauma was found to be associated with HIV-risk behavior. According to the participants, symptoms associated with post-traumatic stress disorder, depression, adjustment disorder, and substance use mediated the relationship between pre-migration trauma and sexual risk behavior. In contrast, a minority of the participants who reported pre-migration trauma but not psychological sequelae, or experienced post-traumatic growth, reported safer sexual practices. It appears that for some individuals, pre-migration trauma resulted in psychiatric sequelae, which may increase an individual's risk to be infected with HIV. Interventions targeted at individuals at increased risk (i.e. pre-migration trauma with unresolved psychiatric symptomatology) may facilitate the prevention of HIV and other sexually transmitted diseases in this population. Integration of multiple psychosocial and health issues is recommended for comprehensive treatment and prevention programs.

Proteome analysis of DNA damage-induced neuronal death using high throughput mass spectrometry.

Isotope-coded affinity tag reagents and high throughput mass spectrometry were used to quantitate changes in the expression of 150 proteins in mouse wild-type (p53(+/+)) cortical neurons undergoing DNA damage-induced death. Immunological techniques confirmed several of the changes in protein expression, but microarray analysis indicated that many of these changes were not accompanied by altered mRNA expression. Proteome analysis revealed perturbations in mitochondrial function, free radical production, and neuritogenesis that were not observed in p53-deficient neurons. Changes in Tau, cofilin, and other proteins recapitulated abnormalities observed in neurodegenerative states in vivo. Additionally, DNA damage caused a p53-dependent decrease in expression of members of the protein kinase A (PKA) signaling pathway. PKA inhibition promoted death in the absence of DNA damage, revealing a novel mechanism by which endogenous down-regulation of PKA signaling may contribute to p53-dependent neuronal death. These data demonstrate the power of high throughput mass spectrometry for quantitative analysis of the neuronal proteome.