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Anna Lipinska, Anna Ledakowicz-Polak, Grzegorz Krauza, Katarzyna Przybylak, Marzenna Zielinska Intensive Cardiac Therapy Clinic, Department of Interventional Cardiology and Electrocardiology, Central Clinical Hospital, Lodz, Poland Background: Wells and Geneva scores are widely used in the assessment of pretest probability of pulmonary embolism (PE). Objective: The objective of this study was to examine the hypothesis that mean platelet volume (MPV) may better predict PE than the clinical prediction rules. Methods: A study was performed among patients with PE. Baseline characteristics and complete blood counts including MPV were prospectively recorded upon admission. To assess clinical probability in patients with PE risk, we used Wells and Geneva scores. Results: Data records of 136 patients (males: 44%) with median age of 66 years (interquartile range [IQR] 57.5–78.0) diagnosed with PE at the Intensive Cardiac Therapy Clinic in Lodz (Poland) were analyzed. Baseline characteristics indicate that patients suffered from arterial hypertension (65%), obesity (32%), and diabetes mellitus (24%). Furthermore, they reported active smoking (21%), prolonged immobilization (20%), major surgery (21%), pregnancy (4%), and oral contraceptives (9%). Patients presented with various symptoms. The MPV, plateletcrit, and D-dimer values on admission were respectively as follows: 10.71 (IQR 3.29–13.67), 0.2 (IQR 0.15–0.24), and 9.23 (IQR 8.5–9.85). The study revealed that Wells score correlated significantly with an elevated MPV value (P0.05). According to our results, there is a lack of coherence between Wells and Geneva scores (P>0.05). Finally, we determined that the optimum MPV level cutoff point for PE on admission with reference to the original Wells score is 9.6 fL. Conclusion: MPV may be considered useful as an adjunctive or independent predictive marker for PE used in lieu of clinical prediction rules. Keywords: pulmonary embolism, mean platelet volume, Wells score, Geneva score

Abstract Background Brown algae belong to the Stramenopiles phylum and are phylogenetically distant from plants and other multicellular organisms. This independent evolutionary history has shaped brown algae with numerous metabolic characteristics specific to this group, including the synthesis of peculiar polysaccharides contained in their extracellular matrix (ECM). Alginates and fucose-containing sulphated polysaccharides (FCSPs), the latter including fucans, are the main components of ECMs. However, the metabolic pathways of these polysaccharides remain poorly described due to a lack of genomic data. Results An extensive genomic dataset has been recently released for brown algae and their close sister species, for which we previously performed an expert annotation of key genes involved in ECM-carbohydrate metabolisms. Here we provide a deeper analysis of this set of genes using comparative genomics, phylogenetics analyses, and protein modelling. Two key gene families involved in both the synthesis and degradation of alginate were suggested to have been acquired by the common ancestor of brown algae and their closest sister species Schizocladia ischiensis. Our analysis indicates that this assumption can be extended to additional metabolic steps, and thus to the whole alginate metabolic pathway. The pathway for the biosynthesis of fucans still remains biochemically unresolved and we also investigate putative fucosyltransferase genes that may harbour a fucan synthase activity in brown algae. Conclusions Our analysis is the first extensive survey of carbohydrate-related enzymes in brown algae, and provides a valuable resource for future research into the glycome and ECM of brown algae. The expansion of specific families related to alginate metabolism may have represented an important prerequisite for the evolution of developmental complexity in brown algae. Our analysis questions the possible occurrence of FCSPs outside brown algae, notably within their closest sister taxon and in other Stramenopiles such as diatoms. Filling this knowledge gap in the future will help determine the origin and evolutionary history of fucan synthesis in eukaryotes.

Traditionally, emotions in dreams have been assessed using subjective ratings by human raters (e.g., external raters or dreamers themselves). These methods have extensive support and utility in dream science, yet they have certain innate limitations due to the subjective nature of the rating methodologies. Attempting to circumvent several of these limitations, we aimed to develop a novel method for objectively classifying and quantifying sequential (word-for-word) emotion within a dream report. We investigated whether sentiment analysis, a branch of natural language processing, could be used to generate continuous positive and negative valence ratings across a dream. In this pilot, proof-of-concept study, we used 14 dream reports collected upon awakening following overnight polysomnography. We also collected pre- and post-sleep affective data and personality metrics. Our objectives included demonstrating that (1) valence ratings derived from sentiment analysis (Valence Aware Dictionary for sEntiment Reasoning [VADER]) could be used to visualize (plot) positive and negative emotion fluctuations within a dream, (2) how the visual properties of emotion fluctuations within a dream (peaks and troughs, area under the curve) can be used to generate novel “emotion indicators” as proxies for emotion regulation throughout a dream, and (3) these emotion indicators correlate with sleep, affective, and personality variables known to be associated with dreaming and emotion regulation. We describe 6 novel, objective dream emotion indicators: Total number of Peaks, total number of Troughs, Positive, Negative, and Overall Emotion Intensity (composites from an “area under the curve” method using the trapezoid rule applied to the peaks and troughs), and the Emotion Gradient (a polynomial trendline fitted to the emotion fluctuations in the dream chart). The latter signifies the overall direction of sequential emotion changes within a dream. Results also showed that ⅚ emotion indicators correlated significantly with at least one existing sleep, affective, or personality variable known to be associated with dreaming and emotion regulation. We propose that the novel emotion indicators potentially serve as proxies for emotion regulation processes unfolding within a dream. These preliminary findings provide a methodological foundation for future studies to test and refine the method in larger and more diverse samples.

Abstract South Africans living in low socioeconomic areas have self-reported unusually long sleep durations (approximately 9–10 h). One hypothesis is that these long durations may be a compensatory response to poor sleep quality as a result of stressful environments. This study aimed to investigate whether fear of not being safe during sleep is associated with markers of sleep quality or duration in men and women. South Africans (n = 411, 25–50 y, 57% women) of African-origin living in an urban township, characterised by high crime and poverty rates, participated in this study. Participants are part of a larger longitudinal cohort study: Modelling the Epidemiologic Transition Study (METS)–Microbiome. Customised questions were used to assess the presence or absence of fears related to feeling safe during sleep, and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index were used to assess daytime sleepiness, sleep quality and insomnia symptom severity respectively. Adjusted logistic regression models indicated that participants who reported fears related to safety during sleep were more likely to report poor sleep quality (PSQI > 5) compared to participants not reporting such fears and that this relationship was stronger among men than women. This is one of the first studies outside American or European populations to suggest that poor quality sleep is associated with fear of personal safety in low-SES South African adults.

Resilience comprises various neurobiological, developmental, and psychosocial components. However, existing measures lack certain critical components, while having limited utility in low-to-middle-income settings. We aimed to develop a reliable and valid measure of resilience encompassing a broad range of components and that can be used across different income settings. We also set out to develop empirical cutoff scores for low, moderate, and high resilience. Results from 686 participants revealed the emergence of three components: positive affect ([alpha] = 0.879), early-life stability ([alpha] = 0.879), and stress mastery ([alpha] = 0.683). Convergent and incremental validity was confirmed using an existing resilience measure as the benchmark. Concurrent validity was also confirmed with significant negative correlations with measures of depression, anxiety, posttraumatic stress disorder, and sleep disruption. Finally, we successfully determined cutoff scores for low, moderate, and high resilience. Results confirm that the Resilience Index is a reliable and valid measure that can be utilized in both high- and low-to-middle-income settings.

IntroductionResearch in the field of cognitive neuroscience has focused on the role of sleep in various neurocognitive processes such as memory consolidation. However, an area that has not been adequately researched is the role of dreaming in this memory process. This study aimed to determine the relationship between affect experienced in dreams and emotional memory consolidation. Considering that REM dreams are laden with emotion and that emotion enhances memory, one possibility is that dream affect could also play a role in emotional memory consolidation. We hypothesised that greater dream-related affect would be associated with greater memory retention of emotional but not neutral information.Methods126 healthy participants, aged 18–35, were recruited for the online study, of which 103 participants had valid data (female: n =73). On the night of the study, participants viewed a series of pictures from the South African Affective Picture System (SA-APS) in an online session. Afterwards, they verbally recalled as many pictures as possible. The following morning, they were asked to recall any dreams and rate the emotional intensity of their dreams. Participants then again verbally recalled all the pictures that they could remember from the previous night.ResultsContrary to the prediction, dream-related affect, regardless of valence, did not predict memory consolidation of positive or negative information. Instead, increases in dream-related affect, and especially anxiety were predictive of better memory retention of all information. The findings also showed that an increase in negative affect in dreams predicted better memory retention of negative information.DiscussionOur results suggest that dream affect is an important modulator of memory consolidation processes occurring during sleep. Furthermore, increased negative affect may indicate which experiences are salient and require consolidation to form long-lasting memories that can guide future behaviour.ConclusionThese findings have implications for psychiatric disorders, such as major depression, which is characterised by negative affect and increased memory sensitivity to negative stimuli.

The receptor tyrosine kinase AXL is associated with epithelial plasticity in several solid tumors including breast cancer and AXL-targeting agents are currently in clinical trials. We hypothesized that AXL is a driver of stemness traits in cancer by co-option of a regulatory function normally reserved for stem cells. AXL-expressing cells in human mammary epithelial ducts co-expressed markers associated with multipotency, and AXL inhibition abolished colony formation and self-maintenance activities while promoting terminal differentiation in vitro. Axl-null mice did not exhibit a strong developmental phenotype, but enrichment of Axl + cells was required for mouse mammary gland reconstitution upon transplantation, and Axl-null mice had reduced incidence of Wnt1-driven mammary tumors. An AXL-dependent gene signature is a feature of transcriptomes in basal breast cancers and reduced patient survival irrespective of subtype. Our interpretation is that AXL regulates access to epithelial plasticity programs in MaSCs and, when co-opted, maintains acquired stemness in breast cancer cells.

IntroductionAcquired cancer therapy resistance evolves under selection pressure of immune surveillance and favors mechanisms that promote drug resistance through cell survival and immune evasion. AXL receptor tyrosine kinase is a mediator of cancer cell phenotypic plasticity and suppression of tumor immunity, and AXL expression is associated with drug resistance and diminished long-term survival in a wide range of malignancies, including NSCLC.MethodsWe aimed to investigate the mechanisms underlying AXL-mediated acquired resistance to first- and third-generation small molecule EGFR tyrosine kinase inhibitors (EGFRi) in NSCLC.ResultsWe found that EGFRi resistance was mediated by up-regulation of AXL, and targeting AXL reduced reactivation of the MAPK pathway and blocked onset of acquired resistance to long-term EGFRi treatment in vivo. AXL-expressing EGFRi-resistant cells revealed phenotypic and cell signaling heterogeneity incompatible with a simple bypass signaling mechanism, and were characterized by an increased autophagic flux. AXL kinase inhibition by the small molecule inhibitor bemcentinib or siRNA mediated AXL gene silencing was reported to inhibit the autophagic flux in vitro, bemcentinib treatment blocked clonogenicity and induced immunogenic cell death in drug-resistant NSCLC in vitro, and abrogated the transcription of autophagy-associated genes in vivo. Furthermore, we found a positive correlation between AXL expression and autophagy-associated gene signatures in a large cohort of human NSCLC (n = 1018).ConclusionOur results indicate that AXL signaling supports a drug-resistant persister cell phenotype through a novel autophagy-dependent mechanism and reveals a unique immunogenic effect of AXL inhibition on drug-resistant NSCLC cells.

BackgroundIndividuals with substance use disorders exhibit maladaptive decision-making on the Iowa Gambling Task (IGT), which involves selecting from card decks differing in the magnitudes of rewards, and the frequency and magnitude of losses. We investigated whether baseline IGT performance could predict responses to contingency management (CM) by treatment-seeking individuals with methamphetamine use disorder (MA Use Disorder) in Cape Town, South Africa.MethodsTwenty-nine individuals with MA Use Disorder underwent an 8-week, escalating reinforcement, voucher-based CM treatment in a study on the suitability of CM therapy for the South African context. Along with 20 healthy control participants, they performed a computerized version of the IGT before starting CM treatment. Seventeen participants maintained abstinence from methamphetamine throughout the trial (full responders), and 12 had an incomplete response (partial responders). Performance on the IGT was scored for magnitude effect (selection of large immediate rewards with high long-term loss) and for frequency effect (preference for frequent rewards and avoidance of frequent losses). Group differences were investigated using linear mixed-effect modeling.ResultsPartial responders made more selections from decks providing large, immediate rewards and long-term losses than healthy controls [p = 0.038, g = -0.77 (-1.09: -0.44)]. Full responders showed a greater, nonsignificant preference for frequent rewards and aversion to frequent losses than partial responders [p = 0.054, g = -0.63 (-0.95: -0.29)].ConclusionsA predilection for choices based on the size and immediacy of reward may reflect a cognitive strategy that works against CM. Pretesting with a decision-making task, such as the IGT, may help in matching cognitive therapies to clients with MA Use Disorder.