CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells

in PLoS ONE (2022)

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a ... [more ▼]

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine/thre onine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines in vitro and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with viability IC50 doses in the range of 0.18–2.6 μM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma cell lines. Further in vivo studies should be performed to determine the treatment potential of CCT196969 in patients with treatment-naïve and resistant melanoma brain metastasis. [less ▲]

Number transcoding in bilinguals—A transversal developmental study

in PLoS ONE (2022), 17(8), 0273391

Number transcoding is the cognitive task of converting between different numerical codes (i.e. visual “42”, verbal “forty-two”). Visual symbolic to verbal transcoding and vice versa strongly relies on ... [more ▼]

Number transcoding is the cognitive task of converting between different numerical codes (i.e. visual “42”, verbal “forty-two”). Visual symbolic to verbal transcoding and vice versa strongly relies on language proficiency. We evaluated transcoding of German-French bilinguals from Luxembourg in 5th, 8th, 11th graders and adults. In the Luxembourgish educational system, children acquire mathematics in German (LM1) until the 7th grade, and then the language of learning mathematic switches to French (LM2). French `70s `80s `90s are less transparent than `30s `40s `50s numbers, since they have a base-20 structure, which is not the case in German. Transcoding was evaluated with a reading aloud and a verbal-visual number matching task. Results of both tasks show a cognitive cost for transcoding numbers having a base-20 structure (i.e. `70s, `80s and `90s), such that response times were slower in all age groups. Furthermore, considering only base-10 numbers (i.e. `30s `40s `50s), it appeared that transcoding in LM2 (French) also entailed a cost. While participants across age groups tended to read numbers slower in LM2, this effect was limited to the youngest age group in the matching task. In addition, participants made more errors when reading LM2 numbers. In conclusion, we observed an age-independent language effect with numbers having a base-20 structure in French, reflecting their reduced transparency with respect to the decimal system. Moreover, we find an effect of language of math acquisition such that transcoding is less well mastered in LM2. This effect tended to persist until adulthood in the reading aloud task, while in the matching task performance both languages become similar in older adolescents and young adults. This study supports the link between numbers and language, especially highlighting the impact of language on reading numbers aloud from childhood to adulthood. [less ▲]

Avoiding bias when inferring race using name-based approaches

in PLoS ONE (2022), 3(17), 0264270

Racial disparity in academia is a widely acknowledged problem. The quantitative understanding of racial-based systemic inequalities is an important step towards a more equitable research system. However ... [more ▼]

Racial disparity in academia is a widely acknowledged problem. The quantitative understanding of racial-based systemic inequalities is an important step towards a more equitable research system. However, because of the lack of robust information on authors’ race, few large-scale analyses have been performed on this topic. Algorithmic approaches offer one solution, using known information about authors, such as their names, to infer their perceived race. As with any other algorithm, the process of racial inference can generate biases if it is not carefully considered. The goal of this article is to assess the extent to which algorithmic bias is introduced using different approaches for name-based racial inference. We use information from the U.S. Census and mortgage applications to infer the race of U.S. affiliated authors in the Web of Science. We estimate the effects of using given and family names, thresholds or continuous distributions, and imputation. Our results demonstrate that the validity of name-based inference varies by race/ethnicity and that threshold approaches underestimate Black authors and overestimate White authors. We conclude with recommendations to avoid potential biases. This article lays the foundation for more systematic and less-biased investigations into racial disparities in science. [less ▲]

Sleep quality and the evolution of the COVID- 19 pandemic in five European countries

in PLoS ONE (2022), 17(12), 0278971

Subjective age, worry and risk-related perceptions in older adults in times of a pandemic

in PLoS ONE (2022), 17(9), 0274293

During the Covid-19 pandemic, older people have been in the spotlight of the public debate. Given their higher risk of severe outcomes of the disease, they have been described as especially vulnerable and ... [more ▼]

During the Covid-19 pandemic, older people have been in the spotlight of the public debate. Given their higher risk of severe outcomes of the disease, they have been described as especially vulnerable and as a burden to others and society. We thus wanted to investigate how older people’s perception of their own age, that is their subjective age, as well as their Covid-19 related risks and worries were related during the pandemic and whether these relationships varied according to participants’ subjective health. We used data from the longitudinal CRISIS study which was conducted in the Grand-Duchy of Luxembourg in June and October 2020. Participants were aged 60–98 and responded on questionnaires regarding their subjective age, worry of falling ill with Covid-19, perceived risk of contracting the virus, perceived risk of falling seriously ill if they contracted Covid-19, as well as their subjective health and covariates. Three cross-lagged panel models were constructed to explore the longitudinal, bidirectional relationships between the variables. Cross-sectionally, a higher subjective age was related to more perceived risk of a serious course of disease. Longitudinally, subjective age and worry did not show any significant association over time, and neither did subjective age and perceived risk of contracting the virus. However, subjective health significantly moderated the relationship of worry and subjective age, showing different trajectories in the relationship depending on whether subjective health was good or bad. Higher perceived risk of falling seriously ill increased subjective age over time. Again, subjective health moderated this relationship: the perceived risk of falling seriously ill affected subjective age only for those with better subjective health. Our findings show the interactive relationship between subjective age and Covid-19 related cognitions and emotions and provide guidance for identifying older people that are most susceptible for negative age-related communication during the pandemic. [less ▲]

Is This Time Really Different? Flight-to-Safety and the COVID-19 Crisis

in PLoS ONE (2021), 16(5),

Dynamical SPQEIR model assesses the effectiveness of non-pharmaceutical interventions against COVID-19 epidemic outbreaks.

in PloS one (2021), 16(5), 0252019

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of ... [more ▼]

Against the current COVID-19 pandemic, governments worldwide have devised a variety of non-pharmaceutical interventions to mitigate it. However, it is generally difficult to estimate the joint impact of different control strategies. In this paper, we tackle this question with an extended epidemic SEIR model, informed by a socio-political classification of different interventions. First, we inquire the conceptual effect of mitigation parameters on the infection curve. Then, we illustrate the potential of our model to reproduce and explain empirical data from a number of countries, to perform cross-country comparisons. This gives information on the best synergies of interventions to control epidemic outbreaks while minimising impact on socio-economic needs. For instance, our results suggest that, while rapid and strong lockdown is an effective pandemic mitigation measure, a combination of social distancing and early contact tracing can achieve similar mitigation synergistically, while keeping lower isolation rates. This quantitative understanding can support the establishment of mid- and long-term interventions, to prepare containment strategies against further outbreaks. This paper also provides an online tool that allows researchers and decision makers to interactively simulate diverse scenarios with our model. [less ▲]

Genome-wide linkage analysis of families with primary hyperhidrosis

in PLoS ONE (2020)

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0–6.1% in the general population, dependent on ... [more ▼]

Primary focal hyperhidrosis (PFH, OMIM %144110) is a genetically influenced condition characterised by excessive sweating. Prevalence varies between 1.0–6.1% in the general population, dependent on ethnicity. The aetiology of PFH remains unclear but an autosomal dominant mode of inheritance, incomplete penetrance and variable phenotypes have been reported. In our study, nine pedigrees (50 affected, 53 non-affected individuals) were included. Clinical characterisation was performed at the German Hyperhidrosis Centre, Munich, by using physiological and psychological questionnaires. Genome-wide parametric linkage analysis with GeneHunter was performed based on the Illumina genome-wide SNP arrays. Haplotypes were constructed using easyLINKAGE and visualised via HaploPainter. Whole-exome sequencing (WES) with 100x coverage in 31 selected members (24 affected, 7 non-affected) from our pedigrees was achieved by next generation sequencing. We identified four genome-wide significant loci, 1q41-1q42.3, 2p14-2p13.3, 2q21.2-2q23.3 and 15q26.3-15q26.3 for PFH. Three pedigrees map to a shared locus at 2q21.2-2q23.3, with a genome-wide significant LOD score of 3.45. The chromosomal region identified here overlaps with a locus at chromosome 2q22.1-2q31.1 reported previously. Three families support 1q41-1q42.3 (LOD = 3.69), two families share a region identical by descent at 2p14-2p13.3 (LOD = 3.15) and another two families at 15q26.3 (LOD = 3.01). Thus, our results point to considerable genetic heterogeneity. WES did not reveal any causative variants, suggesting that variants or mutations located outside the coding regions might be involved in the molecular pathogenesis of PFH. We suggest a strategy based on whole-genome or targeted next generation sequencing to identify causative genes or variants for PFH. [less ▲]

Against mass media trends: Minority growth in cultural globalization

in PLoS ONE (2020)

We investigate the collective behavior of a globalized society under the influence of endogenous mass media trends. The mass media trend is a global field corresponding to the statistical mode of the ... [more ▼]

We investigate the collective behavior of a globalized society under the influence of endogenous mass media trends. The mass media trend is a global field corresponding to the statistical mode of the states of the agents in the system. The interaction dynamics is based on Axelrod’s rules for the dissemination of culture. We find situations where the largest minority group, possessing a cultural state different from that of the predominant trend transmitted by the mass media, can grow to almost half of the size of the population. We show that this phenomenon occurs when a critical number of long-range connections are present in the underlying network of interactions. We have numerically characterized four phases on the space of parameters of the system: an ordered phase; a semi-ordered phase where almost half of the population consists of the largest minority in a state different from that of the mass media; a disordered phase; and a chimera-like phase where one large domain coexists with many very small domains. [less ▲]

Effects of rejection intensity and rejection sensitivity on social approach behavior in women

in PLoS ONE (2020), 15(1), 0227799

Objective: Perceived rejection plays an important role for mental health and social integration. This study investigated the impact of rejection intensity and rejection sensitivity on social approach ... [more ▼]

Objective: Perceived rejection plays an important role for mental health and social integration. This study investigated the impact of rejection intensity and rejection sensitivity on social approach behavior. Method: 121 female participants were randomly assigned to one of three conditions differing in the degree of induced rejection (inclusion, medium rejection, severe rejection). Thereafter they were asked to interact with an unknown person during a touch-based cooperative task. Results: Participants high in rejection sensitivity sought significantly less physical contact than participants low in rejection sensitivity. Individuals in the medium rejection condition touched their partners more often than those in the included condition, while no difference between included and severely rejected participants could be observed. Conclusions: The results suggest that the intensity of rejection matters with regard to coping. While participants in the medium intensity rejection condition aimed to ‘repair’ their social self by seeking increased contact with others, severely rejected participants did not adapt their behavior compared to included participants. Implications for therapy are discussed. [less ▲]