Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.

Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.

Are Inconclusive Decisions in Forensic Science as Deficient as They Are Said to Be?

Many quarters of forensic science use reporting formats such as "identification," "inconclusive," and "exclusion." These types of conclusions express opinions as to whether or not a particular person or object is the source of the material or traces of unknown source that is of interest in a given case. Rendering an "inconclusive" conclusion is sometimes criticized as being inadequate because-supposedly-it does not provide recipients of expert information with helpful directions.

Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis.

Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs) on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis.

On the Bayesian approach to forensic age estimation of living individuals.

Forensic age estimation, a branch of forensic science, has received renewed attention lately mainly due to societal migration phenomena. And yet, the interpretation of age-related evidence is still largely neglected as a field, the literature being usually limited to technical discussions strictly pertaining to the statistical methodologies to be used in estimation process. This short communication aims to highlight the fundamental role of evidence evaluation and interpretation in forensic age estimation.

Tumor-Derived Mesenchymal Stem Cells Use Distinct Mechanisms to Block the Activity of Natural Killer Cell Subsets.

Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression.

Evaluation of Forensic DNA Traces When Propositions of Interest Relate to Activities: Analysis and Discussion of Recurrent Concerns.

When forensic scientists evaluate and report on the probative strength of single DNA traces, they commonly rely on only one number, expressing the rarity of the DNA profile in the population of interest. This is so because the focus is on propositions regarding the source of the recovered trace material, such as "the person of interest is the source of the crime stain." In particular, when the alternative proposition is "an unknown person is the source of the crime stain," one is directed to think about the rarity of the profile.

Whose DNA is this? How relevant a question? (a note for forensic scientists).

This communication seeks to draw the attention of researchers and practitioners dealing with forensic DNA profiling analyses to the following question: is a scientist's report, offering support to a hypothesis according to which a particular individual is the source of DNA detected during the analysis of a stain, relevant from the point of view of a Court of Justice? This question relates to skeptical views previously voiced by commentators mainly in the judicial area, but is avoided by a large majority of forensic scientists. Notwithstanding, the pivotal role of this question has recently been evoked during the international conference "The hidden side of DNA profiles. Artifacts, errors and uncertain evidence" held in Rome (April 27th to 28th, 2012).

A Bayesian network approach to the database search problem in criminal proceedings.

Background: The 'database search problem', that is, the strengthening of a case - in terms of probative value - against an individual who is found as a result of a database search, has been approached during the last two decades with substantial mathematical analyses, accompanied by lively debate and centrally opposing conclusions. This represents a challenging obstacle in teaching but also hinders a balanced and coherent discussion of the topic within the wider scientific and legal community. This paper revisits and tracks the associated mathematical analyses in terms of Bayesian networks.

Health, economy and social capital in Nordic children and their families: a comparison between 1984 and 1996.

Objective: The aim of the study was to analyse the development in the health of children that occurred in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) between 1984 and 1996 and relate it to the changes in economic growth and social capital in these countries during the same period.

Methods: Two cross-sectional studies covered a representative sample of children, aged 2-17 years in each country, a total of 10,291 in 1984 and 10,317 in 1996. The data were collected by mailed questionnaires.

Psychosocial determinants of smoking in Swiss adolescents with special reference to school stress and social capital in schools.

Objectives: To identify the major psychosocial determinants of smoking in adolescents and the school influence on these determinants.

Methods: Cross-sectional questionnaire survey in 8th grade (age 14.8 years, n = 459) of 14 schools.

Social equalization in the health of youth. The role of the school.

Background: A study was made of the role of the school in the process of social equalization in the health of pre-adolescents and adolescents in the city of Bern, Switzerland.

Methods: Questionnaire data obtained from 578 13-year-olds and 476 15-year-olds within the frame of the evaluation of a health-promoting schools project were transformed to 30 indicators of well-being at school, health, emotional well-being, life-skills, and health behaviour and attitudes.

Results: Multiple logistic regression with gender, social class, ethnicity, and school climate as independent variables revealed the disappearance of social gradients by 15 years of age and the emergence of new inequalities related mainly to gender and school climate.

[Arguments and basic principles for continuous monitoring of social differences in the health of Swiss children].

On the basis of the thesis that social inequality has increased during the nineties in all western societies, and that this development is a reason for considerable concern with respect to public health, the authors propose the establishment of a long term monitoring system within the Swiss school health services. A re-analysis of the data obtained in a Swiss epidemiological study of seven-year-olds in the eighties demonstrates that social class was an important determinant of health and development of these children also during a period of economic boom. For various health and developmental problems odds-ratios (lower class vs.

Effect of environmental tobacco smoke exposure on respiratory symptoms in children. SCARPOL Team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution, Climate and Pollen.

Aims: This study determines the prevalence of exposure to environmental tobacco smoke and its relation to respiratory and allergic symptoms among schoolchildren in Switzerland.

Methods: We studied 4470 children aged 6-14 years as part of a multicentre study (SCARPOL study--Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution, Climate and Pollen) conducted in Switzerland between 1992 and 1993. Environmental tobacco smoke exposure, maternal smoking during pregnancy and respiratory symptoms were assessed by means of a self-administered parental questionnaire.

Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution.

Introduction: Lower prevalence rates of allergic diseases in rural as compared with urban populations have been interpreted as indicating an effect of air pollution. However, little is known about other factors of the rural environment which may determine the development of atopic sensitization and related diseases.

Objective: The authors tested the hypothesis that children growing up on a farm were less likely to be sensitized to common aerollergens and to suffer from allergic diseases than children living in the same villages but in nonfarming families.

Comparison of responses to an asthma symptom questionnaire (ISAAC core questions) completed by adolescents and their parents. SCARPOL-Team. Swiss Study on Childhood Allergy and Respiratory Symptoms with respect to Air Pollution.

The primary objective of the study was to determine the impact of the identity of the respondent (parents versus adolescents) on prevalence estimates of asthma symptoms in Swiss adolescents. In addition, factors influencing agreement between parents' and adolescents' responses to the same questions were analysed. One thousand three hundred and seventy-four (78.

Validation of a rhinitis symptom questionnaire (ISAAC core questions) in a population of Swiss school children visiting the school health services. SCARPOL-team. Swiss Study on Childhood Allergy and Respiratory Symptom with respect to Air Pollution and Climate. International Study of Asthma and Allergies in Childhood.

Unlabelled: The primary aim of the study was to assess the validity of the ISAAC core questions on rhinitis in a population of Swiss school children by comparing them to skin prick test results. Second, the positive predictive value in detecting atopy among children with rhinitis symptoms was determined. Third, agreement between parental reports of hay fever and rhinitis symptoms was evaluated, since earlier Swiss prevalence surveys had exclusively relied on reported hay fever.

Respiratory health and long-term exposure to air pollutants in Swiss schoolchildren. SCARPOL Team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution, Climate and Pollen.

The impact of long-term exposure to air pollution on respiratory and allergic symptoms and illnesses was assessed in a cross-sectional study of schoolchildren (ages 6 to 15 yr, n = 4,470) living in 10 different communities in Switzerland. Air pollution measurements (particulate matter less than 10 microns in diameter [PM10], nitrogen dioxide [NO2], sulfur dioxide [SO2], and ozone) and meteorologic data were collected in each community. Reported symptom rates of chronic cough, nocturnal dry cough, and bronchitis, adjusted for individual risk factors, were positively associated with PM10, NO2, and SO2.