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Drinking water and sanitation services in high-income countries typically bring widespread health and other benefits to their populations. Yet gaps in this essential public health infrastructure persist, driven by structural inequalities, racism, poverty, housing instability, migration, climate change, insufficient continued investment, and poor planning. Although the burden of disease attributable to these gaps is mostly uncharacterised in high-income settings, case studies from marginalised communities and data from targeted studies of microbial and chemical contaminants underscore the need for continued investment to realise the human rights to water and sanitation. Delivering on these rights requires: applying a systems approach to the problems; accessible, disaggregated data; new approaches to service provision that centre communities and groups without consistent access; and actionable policies that recognise safe water and sanitation provision as an obligation of government, regardless of factors such as race, ethnicity, gender, ability to pay, citizenship status, disability, land tenure, or property rights.

Supplementary Figures 1-6. Supplementary Fig. 1: ROR1 mRNA expression determined by qRT-PCR correlates with the amount of the surface receptor present on primary CLL cells. Supplementary Fig. 2: Expression of ROR1 in the WNT5A-negative and WNT5Apositive(A), and WNT5B-low and WNT5B-high (B) patient cohorts. Supplementary Fig. 3: A-C) Time-to-first treatment (TTFT) of patient groups stratified based on the expression of WNT5 genes was plotted using Kaplan-Meier survival curves. Supplementary Fig. 4: Expression of WNT5B mRNA levels in patients with TP53 mutations. n.s. - not significant (Mann-Whitney test). Supplementary Fig. 5: A) - C) Expression of surface receptors ROR1, CXCR4 and CCR7 was evaluated by vital staining and flow-cytometry (N=14). Supplementary Fig. 6: Freshly isolated CLL cells were treated as indicated and their migration was analysed using the Transwell assays. Supplementary Materials and Methods

Purpose: ROR1, a receptor in the noncanonical Wnt/planar cell polarity (PCP) pathway, is upregulated in malignant B cells of chronic lymphocytic leukemia (CLL) patients. It has been shown that the Wnt/PCP pathway drives pathogenesis of CLL, but which factors activate the ROR1 and PCP pathway in CLL cells remains unclear.Experimental Design: B lymphocytes from the peripheral blood of CLL patients were negatively separated using RosetteSep (StemCell) and gradient density centrifugation. Relative expression of WNT5A, WNT5B, and ROR1 was assessed by quantitative real-time PCR. Protein levels, protein interaction, and downstream signaling were analyzed by immunoprecipitation and Western blotting. Migration capacity of primary CLL cells was analyzed by the Transwell migration assay.Results: By analyzing the expression in 137 previously untreated CLL patients, we demonstrate that WNT5A and WNT5B genes show dramatically (five orders of magnitude) varying expression in CLL cells. High WNT5A and WNT5B expression strongly associates with unmutated IGHV and shortened time to first treatment. In addition, WNT5A levels associate, independent of IGHV status, with the clinically worst CLL subgroups characterized by dysfunctional p53 and mutated SF3B1. We provide functional evidence that WNT5A-positive primary CLL cells have increased motility and attenuated chemotaxis toward CXCL12 and CCL19 that can be overcome by inhibitors of Wnt/PCP signaling.Conclusions: These observations identify Wnt-5a as the crucial regulator of ROR1 activity in CLL and suggest that the autocrine Wnt-5a signaling pathway allows CLL cells to overcome natural microenvironmental regulation. Clin Cancer Res; 22(2); 459–69. ©2015 AACR.

Aims. Coronavirus disease 2019 is responsible for a worldwide increase in morbidity and mortality. The relationship of this infection to mother-to-child vertical transmission has not been elucidated yet. However, recent reports indicate a foetal death rate of up to 3%. Methods. We report a case of sudden pre-term foetal demise in a woman positive for SARS-CoV-2 but asymptomatic, with physiological course of pregnancy. Results. One of the possible explanations of sudden foetal death may be acute placental insufficiency caused by a SARS-CoV-2 placental infection or the development of foetal inflammatory response syndrome (FIRS). Conclusion. Considering the potential risk of foetal demise, questions remain regarding foetal monitoring and the timing of labour and delivery in the second and third trimesters, particularly in asymptomatic or mild maternal SARS-CoV-2 infection. A relevant multidisciplinary team must also be aware of these risks associated with possibly fatal consequences.

Model predictive control is a popular research topic in the field of motor control. Its direct way of implementing constraints and nonlinearities makes MPC a potential alternative to standard motor control approaches. On the other hand, the control algorithm's dependency on the motor model's precision can make it tricky. Especially when the parameters of the controlled machine change over time. This paper presents a possible solution to a stated problem based on the model adaptivity. Firstly, the connection between experimental data and the parameters change is analyzed. Then, adaptivity schemes are presented. After that, the simulation experiment evaluates the performance of the proposed schemes.

The objective of the present study was to compare the religiosity of the Roma in the 18th century with the present. In 1775 and 1776, Samuel Augustini ab Hortis detailed the way of life of the Roma community in the Austro-Hungarian monarchy in his work “Von dem Heutigen Zustände, Sonderbaren Sitten und Lebensart, Wie Auch von Denen Übrigen Eigenschaften und Umständen der Zigeuner in Ungarn” (On the Contemporary Situation, Distinctive Manners and Way of Life, as Well as the Other Characteristics and Circumstances of Gypsies in Greater Hungary). A detailed content analysis of the part of his work dealing with religion was performed. Subsequently, in 2018, field research was conducted in the environment in which Samuel Augustini lived and worked. It involved six key informants, each representing a different municipality. Data collection was carried out over two periods: in the summer months of 2012–2013 and the winter period of 2018–2019. After the interviews with the key informants, more than 70 participants were included in semi-structured interviews through snowball sampling, and another 40 participants were included in two focus groups. The data was evaluated and content analysis was used to process the data. The findings confirm that both in the past and the present, the Roma community adopted the dominant religion of the host country. In the studied environments, the activities of the majority, present then and now in the Catholic Church, failed, and various other missionary movements, such as the Maranatha Mission, came to the fore. Membership in new religious movements resulted in social changes in marginalized Roma communities. However, they may not have only had positive effects. Various effects of their activities may be studied in the future.

International audience; Next-generation sequencing (NGS) has transitioned from research to clinical routine, yet the comparability of different technologies for mutation profiling remains an open question. We performed a European multicenter (n=6) evaluation of three amplicon-based NGS assays targeting 11 genes recurrently mutated in chronic lymphocytic leukemia. Each assay was assessed by two centers using 48 pre-characterized chronic lymphocytic leukemia samples; libraries were sequenced on the Illumina MiSeq instrument and bioinformatics analyses were centralized. Across all centers the median percentage of target reads ≥100x ranged from 94.2- 99.8%. In order to rule out assay-specific technical variability, we first assessed variant calling at the individual assay level i.e., pairwise analysis of variants detected amongst partner centers. After filtering for variants present in the paired normal sample and removal of PCR/sequencing artefacts, the panels achieved 96.2% (Multiplicom), 97.7% (TruSeq) and 90% (HaloPlex) concordance at a variant allele frequency (VAF) >0.5%. Reproducibility was assessed by looking at the inter-laboratory variation in detecting mutations and 107 of 115 (93% concordance) mutations were detected by all six centers, while the remaining eight variants (7%) were undetected by a single center. Notably, 6 of 8 of these variants concerned minor subclonal mutations (VAF 5%, after rigorous validation, the use of unique molecular identifiers may be necessary to reach a higher sensitivity and ensure consistent and accurate detection of low-frequency variants.

HPVs representing the most common sexually transmitted disease are a group of carcinogenic viruses with different oncogenic potential. The immune system and the vaginal microbiome represent the modifiable and important risk factors in HPV-induced carcinogenesis. HPV infection significantly increases vaginal microbiome diversity, leading to gradual increases in the abundance of anaerobic bacteria and consequently the severity of cervical dysplasia. Delineation of the exact composition of the vaginal microbiome and immune environment before HPV acquisition, during persistent/progressive infections and after clearance, provides insights into the complex mechanisms of cervical carcinogenesis. It gives hints regarding the prediction of malignant potential. Relative high HPV prevalence in the general population is a challenge for modern and personalized diagnostics and therapeutic guidelines. Identifying the dominant microbial biomarkers of high-grade and low-grade dysplasia could help us to triage the patients with marked chances of lesion regression or progression. Any unnecessary surgical treatment of cervical dysplasia could negatively affect obstetrical outcomes and sexual life. Therefore, understanding the effect and role of microbiome-based therapies is a breaking point in the conservative management of HPV-associated precanceroses. The detailed evaluation of HPV capabilities to evade immune mechanisms from various biofluids (vaginal swabs, cervicovaginal lavage/secretions, or blood) could promote the identification of new immunological targets for novel individualized diagnostics and therapy. Qualitative and quantitative assessment of local immune and microbial environment and associated risk factors constitutes the critical background for preventive, predictive, and personalized medicine that is essential for improving state-of-the-art medical care in patients with cervical precanceroses and cervical cancer. The review article focuses on the influence and potential diagnostic and therapeutic applications of the local innate immune system and the microbial markers in HPV-related cancers in the context of 3P medicine.

Financial literacy is becoming one of the key competencies in the 21st century. In its absence, it is virtually impossible to navigate the market for financial products and services and thus ensure financial stability throughout the whole life. The author presents the results of a survey of the financial literacy of young future managers who are currently university students. Based on a questionnaire survey among full-time and part-time students, the author detects the positive impact of the practical experience of external students on their financial literacy. The author uses an innovative metric in the form of a personal finance index to assess financial literacy. In addition to overall success, this approach also makes it possible to analyze knowledge from the eight components of financial literacy. By comparing the results in individual areas, the author reveals that risk management is Achyla's heel of financial literacy. In addition to the knowledge component, the author also deals with the respondents' access to information sources. Based on these findings, the author formulates conclusions for the content of financial education. There is a need for a stronger link between the development of probabilistic thinking and the development of general numeracy with practical financial subjects. An important part of financial education is also the recognition of credible information sources.

Key message Studied organic molecules in Pinus sylvestris L. seem to have acted as a safety net for metal transport, chelation and sequestration, allowing adaptation and growth under highly polluted conditions. Abstract Pinus sylvestris L. is known for its ability to survive in areas of highly elevated metal pollution, such as flotation tailings. The aim of the study was to estimate the content of selected organic molecules (including aliphatic low molecular weight organic acids (ALMWOAs), phenolic compounds and terpenes) and the physiological mechanisms underlying differences in metal/metalloid tolerance of P. sylvestris growing in unpolluted (soil) and polluted (flotation tailings) areas. The dominant ALMWOAs in rhizosphere soil extracts were citric acid followed by malic and oxalic acids, whereas in flotation tailings malic and oxalic acids. In roots and needles, the content of ALMOWAs was significantly higher in P. sylvestris L. tissue from flotation tailings in comparison to soil. Phenolic compounds were detected only in roots and needles, with a generally higher content of nearly all detected compounds from flotation tailings. The composition of roots did not contain all the compounds detected in needles. The profile of needles additionally contained four hydroxybenzoic, protocatechuic and salicylic acids. In pine needles, 24 volatile terpenes were identified in total. The content of these compounds in pine needles from the polluted area was markedly different from the unpolluted area. The dominant volatile monoterpenes in P. sylvestris L. needles from the unpolluted area was three carene, while in pine needles from the polluted area monoterpenes α-pinene was dominant.

Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET). In-silico analysis predicted impaired DNA binding due to W380R mutation. Functional analysis showed that this mutation prevents the ETV6 protein from localizing into the cell nucleus and impairs the transcriptional repression activity of ETV6. Based on the germline ETV6 mutation, ET probably started with somatic JAK2 V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1 IKZF1 gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis.