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Oligodendrocytes are critical for CNS myelin formation and are involved in preterm-birth brain injury (PBI) and multiple sclerosis (MS), both of which lack effective treatments. We present a pharmacogenomic approach that identifies compounds with potent pro-oligodendrogenic activity, selected through a scoring strategy (OligoScore) based on their modulation of oligodendrogenic and (re)myelination-related transcriptional programs. Through in vitro neural and oligodendrocyte progenitor cell (OPC) cultures, ex vivo cerebellar explants, and in vivo mouse models of PBI and MS, we identify FDA-approved leucovorin and dyclonine as promising candidates. In a neonatal chronic hypoxia mouse model mimicking PBI, both compounds promote neural progenitor cell proliferation and oligodendroglial fate acquisition, with leucovorin further enhancing differentiation. In an adult MS model of focal de/remyelination, they improve lesion repair by promoting OPC differentiation while preserving the OPC pool. Additionally, they shift microglia from a pro-inflammatory to a pro-regenerative profile and enhance myelin debris clearance. These findings support the repurposing of leucovorin and dyclonine for clinical trials targeting myelin disorders, offering potential therapeutic avenues for PBI and MS. Effective treatments for myelin repair are currently lacking. Here, the authors show that two FDA-approved drugs, leucovorin and dyclonine, identified through pharmacogenomic screening, promote oligodendrocyte formation and brain repair in myelin injury models. [ABSTRACT FROM AUTHOR]

Background: Although confidence does not automatically imply competence, it does provide pharmacy students with a sense of empowerment to manage a pharmacotherapeutic problem independently. Among the methods used in higher education, there is growing interest in simulation. Aim: To evaluate the impact of simulation on pharmacy students' confidence in performing clinical pharmacy activities. Method: Articles that reported the use of simulation among pharmacy students with fully described outcomes about confidence were included. Studies for which it was impossible to extract data specific to pharmacy students or simulation were excluded. The search was carried out in Medline, Embase, Lissa and PsycInfo from inception to August the 31th, 2022. The results were synthesized into 4 parts: confidence in collecting information, being an expert in a procedure/pathology, counselling and communicating, and other results. The quality assessment of included studies was conducted using the Mixed Methods Appraisal Tool "MMAT" tool. Results: Among the 39 included articles, the majority were published in the last 5 years and conducted in the United States. The majority included pharmacy students in years 1 through 3 (69.2%). The most common study design was the pre-post uncontrolled design (66.7%). Studies measuring the effects of human and/or virtual simulation were mainly focused on confidence to counsel and/or communicate with patients and colleagues (n = 20). Evaluations of the effects of these types of simulation on confidence in information gathering by health professionals were also well represented (n = 16). Conclusion: Simulation-based training generally yielded positive impact on improving pharmacy students' confidence in performing clinical pharmacy activities. Rigorous assessment methods and validated confidence questionnaires should be developed for future studies. [ABSTRACT FROM AUTHOR]

Objectives: Increased risks of central nervous system (CNS) tumors and leukemia associated with computed tomography (CT) exposure during childhood have been reported in recent epidemiological studies. However, no evidence of increased risks was suggested in a previous analysis of the French CT cohort. This study benefits from an updated cohort with a longer follow-up and a larger sample size of patients. Methods: The patients were followed from the date of their first CT (between 2000 and 2011) until their date of cohort exit defined as the earliest among the following: 31 December 2016, date of death, date of first cancer diagnosis or date of their 18th birthday. Cancer incidence, vital status, cancer predisposing factors (PFs), and additional CT scans were collected via external national databases. Hazard ratios (HRs) associated to cumulative organ doses and sex were estimated from Cox models. Results: At the end of follow-up, mean cumulative doses were 27.7 and 10.3 mGy for the brain and the red bone marrow (RBM), respectively. In patients without PFs, an HR per 10 mGy of 1.05 (95% CI: 1.01–1.09) for CNS tumors, 1.17 (95% CI: 1.09–1.26) for leukemia, and 0.96 (95% CI: 0.63–1.45) for lymphoma was estimated. These estimates were not modified by the inclusion of CT scans performed outside the participating hospitals or after the inclusion period. Conclusions: This study shows statistically significant dose-response relationships for CNS tumors and leukemia for patients without PFs. Key Points: • Computed tomography is the most important contributor to the collective dose for diagnostic imaging to the French population. • Concerns have been raised about possible cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children and to their longer life expectancy. • Analysis of the updated French CT cohort shows statistically significant dose-response relationships for CNS tumors and leukemia. [ABSTRACT FROM AUTHOR]

Rickettsia helvetica is an emerging pathogen of the Spotted Fever Group Rickettsia (SFGR) causing spotted fever diseases in various European countries. This tick-borne pathogen replicates in tick tissues such as the midgut and salivary gland, but its potential interactions with the vector microbiota is poorly characterized. The vector microbiome plays a pivotal role in tick-pathogen interactions, and some microbiota members facilitate or impede tick-borne pathogen infection. Manipulations of the tick microbiome have led to reduction in pathogen colonization in the tick vector. However, translating these findings into disease control applications requires a thorough characterization of vector microbiota response to different pathogens. In this study, we analyzed and compared the microbiota of Ixodes ricinus ticks attached on humans and collected in Serbia. Ticks were either infected with R. helvetica, or uninfected with major tick-borne pathogens (referred hereafter as 'pathogen-free'). We used microbial co-occurrence network analysis to determine keystone taxa of each set of samples, and to study the interaction patterns of the microbial communities in response to pathogen infection. The inferred functional profiles of the tick microbiome in R. helvetica-positive and pathogen-free samples were also compared. Our results show that R. helvetica infection reduces significantly the diversity of the microbiota and the connectivity of the co-occurrence network. In addition, using co-occurrence network we identified bacterial taxa (i.e., Enterobacteriaceae, Comamonadaceae, and Bacillus) that were negatively associated with 'Rickettsia' in R. helvetica-infected ticks, suggesting competition between R. helvetica and some members of the tick microbiota. The reconstruction of microbial metabolic pathways shows that the presence of R. helvetica might have a major impact on the metabolic functions of the tick microbiome. These results can inform novel interventions for the prevention of R. helvetica, or other SFGR infections in humans. [ABSTRACT FROM AUTHOR]

Social structures influence human behavior, including their movement patterns. Indeed, latent information about an individual's movement can be present in the mobility patterns of both acquaintances and strangers. We develop a "colocation" network to distinguish the mobility patterns of an ego's social ties from those not socially connected to the ego but who arrive at a location at a similar time as the ego. Using entropic measures, we analyze and bound the predictive information of an individual's mobility pattern and its flow to both types of ties. While the former generically provide more information, replacing up to 94% of an ego's predictability, significant information is also present in the aggregation of unknown colocators, that contain up to 85% of an ego's predictive information. Such information flow raises privacy concerns: individuals sharing data via mobile applications may be providing actionable information on themselves as well as others whose data are absent. Information about an individual's mobility can leave traces embedded in the social network. The authors show that such traces are also present beyond the social network. Simple colocation contains predictive information about one's mobility patterns even when the colocators have no social links. In the aggregate, non-social information can sometimes meet or exceed social information. [ABSTRACT FROM AUTHOR]

This article introduces data collected in the Citizens' Attitudes Under Covid-19 Project (CAUCP), which surveyed public opinion throughout the Covid-19 pandemic in 11 democracies between March and December 2020. In this paper, we present a unique cross-country panel survey of citizens' attitudes and behaviors during a worldwide unprecedented health, governance, and economic crisis. This dataset investigates the behavioral and attitudinal consequences of multifaceted Covid19 crisis across time and contexts. In this paper, we describe the design of the CAUCP and the descriptive features of the dataset; we also present promising research prospects. Measurement(s) Public Opinoin Technology Type(s) Individual-level survey [ABSTRACT FROM AUTHOR]

Background: We assessed trends in infant mortality for Arabic-speakers in Quebec, Canada between 1981 and 2017. Methods: We computed infant mortality rates for Arabic versus French and English-speakers in Quebec over time. We used adjusted risk ratios (aRR) and 95% confidence intervals (CI) to investigate trends among Arabic-speakers according to socioeconomic status, age, and cause of death. Results: Infant mortality rates were 3.0 for Arabic-speakers and 5.1 for French and English-speakers per 1,000 live births. Infant mortality increased for Arabic-speakers between 1989–1995 and 2010-2017 (aRR 2.07; 95% CI, 1.04–4.12), but decreased for French and English-speakers (aRR 0.77; 95% CI, 0.73–0.81). The increase in infant mortality was greater for socioeconomically advantaged Arabic-speakers (aRR 2.52; 95% CI, 1.20–5.28) and early neonatal mortality (aRR 1.64; 95% CI, 0.98–2.76). Discussion: Arabic-speakers in Quebec have a lower risk of infant mortality than French and English-speakers, but increasing infant mortality among Arabic-speakers is narrowing the gap. [ABSTRACT FROM AUTHOR]

The impact of pesticides on health is a major public health concern. A higher risk to develop chronic lymphoid malignancies has been demonstrated to be associated with occupational pesticide exposure (OPE). By contrast, little is known of the impact of OPE on the occurrence of myeloid malignancies especially acute myeloid leukemia (AML). The purpose of this meta-analysis is to summarize data on the association between OPE and AML. A relevant dataset of case–control studies was extracted. Among 6784 references extracted, 14 were selected, representing 3,955 AML patients and 9,948 control subjects diagnosed between 1976 and 2010. An adverse association was found between OPE and AML (OR = 1.51; 95%CI: 1.10–2.08), not affected by sensitivity analyses. Funnel plot asymmetry suggested a publication bias underestimating OR. Stratified analysis showed the association to be driven by studies with: (1) monocentric AML patients and hospital-based control population, (2) Newcastle–Ottawa scale > 6 and the group of studies identified as with the lowest risk, (3) exposure assessment through peer-to-peer interview, (4) diagnosis in North America and Asia and after 1995, (5) restriction to de novo AML. Moreover, the association between OPE and AML was significant with insecticides. These findings broaden the spectrum of pesticide toxicity to myeloid malignancies. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (Group B Streptococcus, GBS), is a frequent human colonizer and a leading cause of neonatal meningitis as well as an emerging pathogen in non-pregnant adults. GBS possesses a broad animal host spectrum, and recent studies proved atypical GBS genotypes can cause human invasive diseases through animal sources as food-borne zoonotic infections. We applied a MALDI-TOF MS typing method, based on molecular weight variations of predefined 28 ribosomal subunit proteins (rsp) to classify GBS strains of varying serotypes into major phylogenetic lineages. A total of 249 GBS isolates of representative and varying capsular serotypes from patients and animal food sources (fish and pig) collected during 2016–2018 in Hong Kong were analysed. Over 84% (143/171) noninvasive carriage GBS strains from patients were readily typed into 5 globally dominant rsp-profiles. Among GBS strains from food animals, over 90% (57/63) of fish and 13% (2/15) of pig GBS matched with existing rsp-profiles, while the remainder were classified into two novel rsp-profiles and we failed to assign a fish strain into any cluster. MALDI-TOF MS allowed for high-throughput screening and simultaneous detection of novel, so far not well described GBS genotypes. The method shown here is rapid, simple, readily transferable and adapted for use in a diagnostic microbiology laboratory with potential for the surveillance of emerging GBS genotypes with zoonotic potential. [ABSTRACT FROM AUTHOR]

The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that aimed to compare the outcome of patients diagnosed with any histological subtype of lymphoma associated with hypercalcemia, at diagnosis or relapse, with a group of controls matched for histological and prognostic factors. Sixty-two and 118 comparable patients treated between 2000 and 2016 were included in hypercalcemia and control cohorts, respectively. Hypercalcemia was found mainly at diagnosis (71%) in higher-risk patients (prognosis scores ≥ 3, 76%) and those with diffuse large B cell lymphoma (67.7%), stage III/IV disease (91.9%), and elevated LDH (90.3%). Two-year progression-free survival (PFS) was shorter in the hypercalcemia than control cohort [30.1% (95% confidence interval (95% CI) 18.3-41.9) vs 63.9% (95% CI 5.1-72.7), p < 0.001]. Two-year overall survival (OS) was 40.6% (95% CI 28.1-53.1) and 77.7% (95% CI 70.1-85.3) in the hypercalcemia and control cohorts, respectively (p < 0.001). Hypercalcemia was independently associated with poor PFS [HR = 2.5 (95% CI 1.4-3.5)] and OS [HR = 4.7 (95% CI 2.8-7.8)] in multivariate analysis. Among the 40 patients who received autologous stem cell transplantation (ASCT), hypercalcemia was still associated with shorter OS [2-year OS: 65% (95% CI 40.1-89.9) vs 88.0 (95% CI 75.3-100), p = 0.04]. Hypercalcemia may be associated with chemo-resistance, given its impact on PFS and OS. Hence, these data suggest that alternate strategies for lymphoma patients with hypercalcemia should be developed. [ABSTRACT FROM AUTHOR]

Code quality is a constant challenge faced by today's software industry. To ensure that developers follow good coding practices, a variety of program analysis and test coverage tools are routinely deployed. However, these tools often fail to engage and change the practices of developers when applied to legacy systems as they output a huge number of warnings, quickly overwhelming the developers. In this article, we explore how individual feedback and gamification can motivate developers to pay more attention to good coding practices. To that extent, we implemented these two concepts in a tool that we deployed at two large companies where we conducted a case study. We find out that individual feedback is essential for motivating developers. We also find that gamification can be useful but has to be used with caution as it can frustrate some developers. Finally, we reflect on some lessons learned during our case studies, and conclude that the promising approach of our tool needs to be supported by longitudinal studies as well as comparative studies. [ABSTRACT FROM AUTHOR]

The coexistence of dual hematological neoplasms is very rare. Sequential or synchronous neoplasms in hematology are an uncommon and complex clinical situation. The aim of the Hemo2 study was to describe the clinical characteristics and analyze the outcome of these patients. We performed a retrospective review of all patients diagnosed with sequential or synchronous hematological malignancies in the university hospital of Tours, between 2007 and 2018. We identified 49 patients in our study, with a prevalence of 0.89%. Sequential and synchronous combinations were found in 36 (73%) and 13 (27%) patients, respectively. One patient presented three sequential neoplasms. The median cumulative incidence was 6 years (95% CI 3-7). Among all neoplasms diagnosed (n = 99), we found 79 lymphoid neoplasms (LNs) (80%) and 20 myeloid neoplasms (MNs) (20%). Sex ratio was 1.88 with 65% of males and 35% of females. The most common LNs were Hodgkin lymphoma (n = 16; 16%) and multiple myeloma (n = 11; 11%). The most frequent MN was essential thrombocythemia (n = 5; 5%). The most common combination was Hodgkin lymphoma and follicular lymphoma in five (10%) patients. The overall survival from the first diagnosis (OS1) at 5 years was 82.4% (95% CI 72.1-94.3). The median overall survival from the second diagnosis (OS2) was 98 months (95% CI 44-NR) and 5-year OS2 was 58.7% (95% CI 45.5-75.7). Median progression-free survival from the second diagnosis (PFS) was 47 months (95% CI 27-NR) with 5-year PFS of 49% (95% CI 35.9-67). OS and PFS did not statistically differ between synchronous and sequential dual neoplasms. In this cohort, that the death relative risk (RR) was significantly lower if the second neoplasm appeared after more than 4 years following the first diagnosis (OR 0.37 (95% CI 0.16-0.90)). The Hemo2study confirmed the rarity of dual hematological neoplasms. In this cohort, HL and FL were the most frequent combinations. Our results may support that synchronous and sequential dual neoplasms bear the same prognosis. Further studies are needed to better characterize these uncommon clinical situations. [ABSTRACT FROM AUTHOR]

We aimed to identify factors associated with unfavorable outcome in patients treated for infective endocarditis (IE), with a focus on departure from European guidelines. We conducted a retrospective audit of all adult patients treated for endocarditis during a 1-year period across a regional network of nine care centers in the south-east of France. Medical records were reviewed regarding patient and infection characteristics, antibiotic therapy, outcome, and compliance to the European Society of Cardiology guidelines. Antibiotic treatment appropriateness was evaluated regarding molecule, dosage, and duration, according to guidelines. Primary endpoint was the assessment of factors associated with unfavorable outcome, defined as in-hospital mortality or IE relapse at 1-year follow-up. Secondary endpoints were intensive care admission, iatrogenic events, and nosocomial infections that occurred during hospital stay. One hundred patients were included. Median age was 71 years old. Twenty-two patients died and IE relapse occurred in two patients, representing 24 patients with unfavorable outcome. Overall, antibiotic treatment was deemed appropriate in 28 cases. Thirty-three patients required intensive care, 34 iatrogenic events were found, including 19 acute kidney injuries, and 13 nosocomial infections occurred during care. Using a logistic regression, factors associated with unfavorable outcome were admission in the intensive care unit (adjusted odd ratio 7.26 [1.8-29.28]; p = 0.005), new-onset nosocomial infection (adjusted odd ratio 8.83 [1.42-54.6]; p = 0.019), and age > 71 years old (adjusted odd ratio 11.2 [2.76-46.17]; p < 0.001). Departure from guidelines was frequent but not related to unfavorable outcome in our study. Only intensive care, age, and nosocomial infections were associated with mortality and relapse. Iatrogenic events were numerous, with no impact on outcome. [ABSTRACT FROM AUTHOR]

The increasing importance of performance-based earthquake engineering analysis points out the necessity to assess quantitatively the risk of liquefaction of embankment-type structures. In this extreme scenario of soil liquefaction, devastating consequences are observed, e.g., excessive settlements, lateral spreading and slope instability. The present work discusses the global dynamic response and interaction of an earth structure-foundation system, so as to determine quantitatively the collapse mechanism due to foundation’s soil liquefaction. A levee-foundation system is simulated, and the influence of characteristics of input ground motion, as well as of the position of liquefied layer on the liquefaction-induced failure, is evaluated. For the current levee model, its induced damage level (i.e., induced crest settlements) is strongly related to both liquefaction apparition and dissipation of excess pore water pressure on the foundation. The respective role of input ground motion characteristics is a key component for soil liquefaction apparition, as long duration of mainshock can lead to important nonlinearity and extended soil liquefaction. A circular collapse surface is generated inside the liquefied region and extends toward the crest in both sides of the levee. Even so, when the liquefied layer is situated in depth, no significant effect on the levee response is found. This research work provides a reference case study for seismic assessment of embankment-type structures subjected to earthquake and proposes a high-performance computational framework accessible to engineers. [ABSTRACT FROM AUTHOR]

The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical areas worldwide, affecting hundreds of millions of people each year. Dengue viruses are typically transmitted by mosquitoes and can cause a wide range of symptoms from flu-like fever to organ impairment and death. Although conventional diagnostic tests can provide early diagnosis of acute dengue infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop affordable, simple, rapid, and robust diagnostic tools that can be used at ‘Point of Care’ settings. Early diagnosis is crucial to improve patient management and reduce the risk of complications. In the present study, a novel laser-cut device made of glass-fiber paper was designed and tested for the detection of the dengue Non Structural 1 (NS1) viral protein and specific IgM in blood and plasma. The device, called PAD, was able to detect around 25 ng/mL of NS1 protein in various sample types in 8 minutes, following a few simple steps. The PAD was also able to detect specific IgM in human plasmas in less than 10 minutes. The PAD appears to have all the potential to assist health workers in early diagnosis of dengue fever or other tropical fevers caused by flaviviruses. [ABSTRACT FROM AUTHOR]

Purpose: At the global scale, gardening activities are often performed in urban areas with a historical background of pollution. In this study, a participatory program was developed with citizens concerned by gardening activities near a 50-year-old regulated lead recycling company, with the aim of co-constructing the tools for the assessment and management of potential sanitary risks induced by historic pollution with persistent (eco) toxic metals: lead and cadmium. Materials and methods: Soils and vegetables (lettuce, leek, celery, carrot, chard, pumpkin, and celeriac) samples were collected from four kitchen gardens neighboring a 50-year-old secondary lead smelter. Both total and in vitro human bioaccessible metal concentrations in the cultivated plants were measured in relation to soil characteristics. Results and discussion: The results showed that the soils of these gardens were slightly contaminated by metals (Pb, 77 to 236 mg kg; and Cd, 0.5 to 1 mg kg) in comparison with the natural geologic background. However, significant pollution of vegetables can occur especially with lead (Pb up to 9.8 mg kg in lettuce) and certainly as a result of direct foliar transfer. The washing of plants before consumption is therefore recommended in the context of atmospheric fallout of ultrafine particles enriched with metals. Conclusions: Metal bioaccessibility measure integrates the influence of metal type, plant type, and soil physico-chemical properties. Based on the results, it is proposed that human bioaccessible fraction of metals may also be currently taken into account as well as total metal quantities and bioaccumulation factors in risk assessment studies performed in gardens. Overall, this study has led to reflections and functional recommendations aimed at reducing human exposure and to finally developing sustainable gardening practices. [ABSTRACT FROM AUTHOR]

Decentralization has been put forward as a powerful tool to reduce poverty and improve governance in Africa. This paper will study the existence and identify the nature of spillovers resulting from local expenditure policies. These spillovers impact the efficiency of decentralization. We develop a two-jurisdiction model of public expenditure, which differs from existing literature by capturing the extreme poverty of some local governments in developing countries through a generalized notion of Nash equilibrium, namely constrained Nash equilibrium. We show how and under what conditions spillovers among jurisdictions induce strategic behaviors from local officials. By estimating a spatial lag model for a panel data analysis of the 77 communes in Benin from 2002 to 2008, our empirical analysis establishes the existence of the strategic complementarity of public spending in various jurisdictions. Thus, any increase in the local public provision in one jurisdiction should induce a similar variation among the neighboring jurisdictions. This result raises the issue of coordination among local governments, and more broadly, it questions the efficiency of decentralization in developing countries in line with Oates' theorem. [ABSTRACT FROM AUTHOR]

At the global scale, high concentrations of particulate matter (PM) enriched with metal(loid)s are currently observed in the atmosphere of urban areas. Foliar lead uptake was demonstrated for vegetables exposed to airborne PM. Our main objective here was to highlight the health risk associated with the consumption of vegetables exposed to foliar deposits of PM enriched with the various metal(loid)s frequently observed in the atmosphere of urban areas (Cd, Sb, Zn and Pb). Leaves of mature cabbage and spinach were exposed to manufactured mono-metallic oxide particles (CdO, SbO and ZnO) or to complex process PM mainly enriched with lead. Total and bioaccessible metal(loid) concentrations were then measured for polluted vegetables and the various PM used as sources. Finally, scanning electronic microscopy coupled with energy dispersive X-ray microanalysis was used to study PM-phyllosphere interactions. High quantities of Cd, Sb, Zn and Pb were taken up by the plant leaves. These levels depended on both the plant species and nature of the PM, highlighting the interest of acquiring data for different plants and sources of exposure in order to better identify and manage health risks. A maximum of 2 % of the leaf surfaces were covered with the PM. However, particles appeared to be enriched in stomatal openings, with up to 12 % of their area occupied. Metal(loid) bioaccessibility was significantly higher for vegetables compared to PM sources, certainly due to chemical speciation changes. Taken together, these results confirm the importance of taking atmospheric PM into account when assessing the health risks associated with ingestion of vegetables grown in urban vegetable crops or kitchen gardens. [ABSTRACT FROM AUTHOR]