Evaluation of alcohol consumption motivation: psychometric properties of the Alcohol Consumption Motivation Inventory by V.Yu. Zavyalov

The alcohol consumption motivation inventory (ACM) was developed by V.Yu. Zavyalov. Now it is a widespread psychometric tool in research and clinical practice for the evaluation of alcohol consumption motivation in Russian-speaking patients with alcohol use disorders. The aim of the study is to analyze the psychometric properties of the ACM inventory. Results show that the factor structure of the ACM inventory significantly differs from the one stated in the original. The results of the statistical analysis allowed three significant clusters. Cluster A was composed of the scales of the conditioned triad—traditional, submissive, and pseudo-cultural motives. This cluster also partially included hedonistic motives and self-harm motives. Cluster B was composed of scales of personal and pathological triads—withdrawal, ataractic and hyperactivational motives. Hedonistic motives and addictive motives were also partially included. Cluster B included self-harm motives and hangover (addictive) motives. According to the data obtained, the ACM inventory cannot measure an alcohol consumption motivation in the way of the original method. Future work on the modification of the ACM inventory should be based on the results obtained recently in neurophysiological and clinicalpsychopharmacological studies in the field of motivation for alcohol consumption, and includes the revision of the items of the questionnaire, a statistically substantiated gradation of levels for assessing the effectiveness of the motives for alcohol use, and the validation of the version of the ACM questionnaire in women sample.

Os impactos do COVID-19 no consumo de bens básicos e suas implicações na gestão da logística urbana

O objetivo desta pesquisa é caracterizar o comportamento do consumidor e a percepção do lojista quanto às compras de suprimentos básicos, antes e durante o COVID-19, assim como relacionar os comportamentos e percepções dos agentes com os desafios da logística urbana de abastecimento do mercado. Foram aplicados dois questionários em regiões classificadas como BOP (Base of Pyramid) e feitas análises descritivas e multivariadas por meio da análise de cluster. A pesquisa mostra que há um aumento na frequência de compra dos consumidores no período de pandemia, o que aumenta também a demanda dos lojistas e as necessidades logísticas das regiões, que apresentam-se debilitadas principalmente pela falta de vagas para carga e descarga e infraestrutura viária. Os resultados mostram que houve um aumento de compras por aplicativos de entrega durante a pandemia e que parece ser uma tendência, o que poderá exigir dessas regiões uma melhor infraestrutura viária para veículos de grande porte (usados por fornecedores) e veículos leves (usados por entregadores).

m6A function and tumor microenvironment infiltration characteristics in glioma

Background Most studies related to N6-methyladenosine (m6A) in glioma have been conducted only at the single-gene level, while the m6A modification patterns and correlation between m6A and immune cells’ tumor microenvironment infiltration have not been comprehensively reported. Methods Eighty-five clinical samples were obtained from the Gene Expression Omnibus; another 599 clinical samples and 174 transcriptome data were obtained from The Cancer Genome Atlas. Based on data analysis using the R program and principal component analysis, we established an m6Ascore quantitative scoring system and analyzed the modification of 22 m6A-related genes with TME infiltration characteristics. Results Three m6A modification patterns and the characteristics of immune cell infiltration were identified. Cluster A corresponded to the immune-desert phenotype, cluster B corresponded to the immune-excluded phenotype, and cluster C corresponded to the immune-inflamed phenotype. Cluster B showed the worst long-term prognosis, whereas cluster A had the best long-term prognosis. Anti-CD52/HE5 shows potential as an immune therapy for glioma. Conclusions This research provides a foundation for understanding m6A modification patterns in glioma and a potential prognostic biomarker and immune therapy target for treat glioma.

Tracing a Black Hole: Probing Cosmic Darkness in Anthropocenic Times

In April 2019, the Event Horizon Telescope (EHT) project released an unprecedented image of a supermassive black hole at the centre of galaxy Messier 87. The image, which shows a dark disc outlined by swirling hot gas circling the black hole’s event horizon, exhibits a 55 million-year-old cosmic event in the Virgo galaxy cluster—a void of stellar mass measuring some 6.5 billion times that of our sun. Situated within today’s (Good) Anthropocene scenario, characterized as it is by both the rise of an inhospitable planet but also a range of good vibes and affirmative mantras, this tracing explores this newly “discovered” black hole in terms of the unthinkable questions and speculative trajectories it raises for education and its futures. Through a series of forays into astrophysics, historical examples of cosmic imaging, and further exploration of the image created by EHT, this tracing outlines the black hole and its apparent horizons in order to propose a strange vantage point from which pedagogical problem-posing might be interrupted, mutated, and relaunched. By turning to that which lies outside of the traditional science classroom—beyond the school, beyond curriculum, indeed, beyond the planet itself—this tracing seeks to probe this black hole event in terms of its weird and weirding pedagogical trajectories so as to speculate on unthought possibilities for resituating (science) education in the age of the Anthropocene.

Prognostic Immunophenotyping Clusters of Clear Cell Renal Cell Carcinoma Defined by the Unique Tumor Immune Microenvironment

Background: The tumor microenvironment affects the occurrence and development of cancers, including clear cell renal cell carcinoma (ccRCC). However, how the immune contexture interacts with the cancer phenotype remains unclear.Methods: We identified and evaluated immunophenotyping clusters in ccRCC using machine-learning algorithms. Analyses for functional enrichment, DNA variation, immune cell distribution, association with independent clinicopathological features, and predictive responses for immune checkpoint therapies were performed and validated.Results: Three immunophenotyping clusters with gradual levels of immune infiltration were identified. The intermediate and high immune infiltration clusters (Clusters B and C) were associated with a worse prognosis for ccRCC patients. Tumors in the immune-hot Clusters B and C showed pro-tumorigenic immune infiltration, and these patients showed significantly worse survival compared with patients in the immune-cold Cluster A in the training and testing cohorts (n = 422). In addition to distinct immune cell infiltrations of immunophenotyping, we detected significant differences in DNA variation among clusters, suggesting a high degree of genetic heterogeneity. Furthermore, expressions of multiple immune checkpoint molecules were significantly increased. Clusters B and C predicted favorable outcomes in 64 ccRCC patients receiving immune checkpoint therapies from the FUSCC cohort. In 360 ccRCC patients from the FUSCC validation cohort, Clusters B and C significantly predicted worse prognosis compared with Cluster A. After immunophenotyping of ccRCC was confirmed, significantly increased tertiary lymphatic structures, aggressive phenotype, elevated glycolysis and PD-L1 expression, higher abundance of CD8+ T cells, and TCRn cell infiltration were found in the immune-hot Clusters B and C.Conclusion: This study described immunophenotyping clusters that improved the prognostic accuracy of the immune contexture in the ccRCC microenvironment. Our discovery of the novel independent prognostic indicators in ccRCC highlights the relationship between tumor phenotype and immune microenvironment.

Structural insight on the mechanism of an electron-bifurcating [FeFe] hydrogenase

Electron-bifurcation is a fundamental energy conservation mechanism in nature. The electron-bifurcating [FeFe] hydrogenase from Thermotoga maritima (HydABC) requires both NADH and ferredoxin to reduce protons generating hydrogen. The mechanism of electron-bifurcation in HydABC remains enigmatic primarily due to the lack of structural information. Here, we present a 2.3 Å electron cryo-microscopy structure of HydABC. The structure is a heterododecamer composed of two independent ‘halves’ each made of two strongly interacting HydABC heterotrimers electrically connected via a [4Fe-4S] cluster. A central electron transfer pathway connects the active sites for NADH oxidation and proton reduction. Symmetry expansion identified two conformations of a flexible iron-sulfur cluster domain: a “closed bridge” and an “open bridge” conformation, where a Zn2+ site may act as a “hinge” allowing domain movement. Based on these structural revelations, we propose two new mechanisms of electron-bifurcation in HydABC.

The impact of high-risk medications on mortality risk among older adults with polypharmacy: evidence from the English Longitudinal Study of Ageing

Background Polypharmacy is common among older people and is associated with an increased mortality risk. However, little is known about whether the mortality risk is related to specific medications among older adults with polypharmacy. This study therefore aimed to investigate associations between high-risk medications and all-cause and cause-specific mortality among older adults with polypharmacy. Methods This study included 1356 older adults with polypharmacy (5+ long-term medications a day for conditions or symptoms) from Wave 6 (2012/2013) of the English Longitudinal Study of Ageing. First, using the agglomerative hierarchical clustering method, participants were grouped according to the use of 14 high-risk medication categories. Next, the relationship between the high-risk medication patterns and all-cause and cause-specific mortality (followed up to April 2018) was examined. All-cause mortality was assessed by Cox proportional hazards model and competing-risk regression was employed for cause-specific mortality. Results Five high-risk medication patterns—a renin-angiotensin-aldosterone system (RAAS) inhibitors cluster, a mental health drugs cluster, a central nervous system (CNS) drugs cluster, a RAAS inhibitors and antithrombotics cluster, and an antithrombotics cluster—were identified. The mental health drugs cluster showed increased risks of all-cause (HR = 1.55, 95%CI = 1.05, 2.28) and cardiovascular disease (CVD) (SHR = 2.11, 95%CI = 1.10, 4.05) mortality compared with the CNS drug cluster over 6 years, while others showed no differences in mortality. Among these patterns, the mental health drugs cluster showed the highest prevalence of antidepressants (64.1%), benzodiazepines (10.4%), antipsychotics (2.4%), antimanic agents (0.7%), opioids (33.2%), and muscle relaxants (21.5%). The findings suggested that older adults with polypharmacy who took mental health drugs (primarily antidepressants), opioids, and muscle relaxants were at higher risk of all-cause and CVD mortality, compared with those who did not take these types of medications. Conclusions This study supports the inclusion of opioids in the current guidance on structured medication reviews, but it also suggests that older adults with polypharmacy who take psychotropic medications and muscle relaxants are prone to adverse outcomes and therefore may need more attention. The reinforcement of structured medication reviews would contribute to early intervention in medication use which may consequently reduce medication-related problems and bring clinical benefits to older adults with polypharmacy.