Unveiling the Complexity of Rearrangements in Acute Myeloid Leukemias with Optical Genome Mapping.

rearrangements are major genetic entities in the classification of acute myeloid leukemias (AMLs), but their diverse and frequently cryptic nature makes their detection and characterization challenging. Karyotypic anomalies at the locus and/or abnormal Fluorescence in situ hybridization (FISH) results strongly indicate a fusion, but the identification of the translocation partner gene often requires further investigation. partial tandem duplications (PTDs), on the other hand, are undetectable by standard cytogenetics methods.

Private groundwater contamination and risk management: A comparative scoping review of similarities, drivers and challenges across two socio-economically developed regions.

Consolidation of multi-domain risk management research is essential for strategies facilitating the concerted government (educational) and population-level (behavioural) actions required to reduce microbial private groundwater contamination. However, few studies to date have synthesised this literature or sought to ascertain the causal generality and extent of supply contamination and preventive responses. In light of the Republic of Ireland (ROI) and Ontario's high reliance and research focus on private wells and consequent utility for empirical comparison, a scoping review of pertinent literature (1990-2022) from both regions was undertaken.

DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML.

Monosomy 5 and deletions of the chromosome 5q (-5/del(5q)) are recurrent events in de novo adult acute myeloid leukemia (AML), reaching up to 40% of cases in secondary AML. These chromosome anomalies are associated with TP53 mutations and with very poor prognosis. Using the large Leucegene genomic and transcriptomic dataset composed of 48 -5/del(5q) patient specimens and 367 control AML, we identified DELE1 - located in the common deleted region - as the most consistently downregulated gene in these leukemias.

Integrating consumer risk perception and awareness with simulation-based quantitative microbial risk assessment using a coupled systems framework: A case study of private groundwater users in Ontario.

Private well users in Ontario are responsible for ensuring the potability of their own private drinking water source through protective actions (i.e., water treatment, well maintenance, and regular water quality testing).

Classification of sub-populations for quantitative risk assessment based on awareness and perception: A cross-sectional population study of private well users in Ontario.

Private well users in Ontario are responsible for protective actions, including source maintenance, treatment, and submitting samples for laboratory testing. However, low participation rates are reported, thus constituting a public health concern, as risk mitigation behaviours can directly reduce exposure to waterborne pathogens. The current study examined the combined effects of socio-demographic profile, experience(s), and "risk domains" (i.

Impacts of COVID-19 lockdown on private domestic groundwater sample numbers, E. coli presence and E. coli concentration across Ontario, January 2020-March 2021: An interrupted time-series analysis.

Approximately 1.5 million individuals in Ontario are supplied by private water wells (private groundwater supplies). Unlike municipal supplies, private well water quality remains unregulated, with owners responsible for testing, treating, and maintaining their own water supplies.

Private groundwater contamination and extreme weather events: The role of demographics, experience and cognitive factors on risk perceptions of Irish private well users.

Extreme weather events (EWEs) may significantly increase pathogenic contamination of private (unregulated) groundwater supplies. However, due to the paucity of protective guidance, private well users may be ill-equipped to undertake adaptive actions. With rising instances of waterborne illness documented in groundwater-dependent, developed regions such as the Republic of Ireland, a better understanding of well user risk perceptions pertaining to EWEs is required to establish appropriate educational interventions.

Drinking Water Consumption Patterns among Private Well Users in Ontario: Implications for Exposure Assessment of Waterborne Infection.

Understanding the water consumption patterns within a specific population informs development of increasingly accurate, spatially specific exposure and/or risk assessment of waterborne infection. The current study examined the consumption patterns of private well users in Ontario while considering potentially influential underlying sociodemographics, household characteristics, and experiential factors. A province-wide online survey was circulated between May and August 2018 (n = 1,162).

Examining influential drivers of private well users' perceptions in Ontario: A cross-sectional population study.

Private well users are responsible for managing and maintaining the quality of their drinking water source. Previous studies in Canada have reported low testing rates among well users, a cornerstone of well stewardship behaviours that can prevent the consumption of contaminated groundwater. To improve well stewardship, it is important to understand the interactions between, and the impacts of, various factors that may influence behaviours.

Genetic characterization of ABT-199 sensitivity in human AML.

Acute myeloid leukemias (AML) with mutations in the NPM1 gene (NPM1c+) represent a large AML subgroup with varying response to conventional treatment, highlighting the need to develop targeted therapeutic strategies for this disease. We screened a library of clinical drugs on a cohort of primary human AML specimens and identified the BCL2 inhibitor ABT-199 as a selective agent against NPM1c+ AML. Mutational analysis of ABT-199-sensitive and -resistant specimens identified mutations in NPM1, RAD21, and IDH1/IDH2 as predictors of ABT-199 sensitivity.

Rapid cold hardening and octopamine modulate chill tolerance in Locusta migratoria.

Temperature has profound effects on the neural function and behaviour of insects. When exposed to low temperature, chill-susceptible insects enter chill coma, a reversible state of neuromuscular paralysis. Despite the popularity of studying the effects of low temperature on insects, we know little about the physiological mechanisms controlling the entry to, and recovery from, chill coma.

Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition.

Patients diagnosed with acute myeloid leukemia with complex karyotype (CK AML) have an adverse prognosis using current therapies, especially when accompanied by alterations. We hereby report the RNA-sequencing analysis of the 68 CK AML samples included in the Leucegene 415 patient cohort. We confirm the frequent occurrence of alterations in this subgroup and further characterize the allele expression profile and transcript alterations of this gene.

Dispositional mindfulness attenuates the emotional attentional blink.

Emotional stimuli have been shown to automatically hijack attention, hindering the detection of forthcoming targets. Mindfulness is defined as a present moment non-judgemental attentional stance that can be cultivated by meditation practices, but that may present interindividual variability in the general population. The mechanisms underlying modification in emotional reactivity linked to mindfulness are still a matter of debate.

Current Practices and Challenges in Method Validation.

Method validation is a cornerstone on which biomarker development and utilization rest. However, given the abundance of biomarker candidates that are being identified and characterized, validation of these entities for the use in nonclinical studies can be complex. The objective of this continuing education course was to review current practices and challenges encountered during the validation of methods for the analysis of novel biomarkers.

A new approach for safe planning transfer using semi-automatically adjustable instrument guides.

Accurate planning transfer is a prerequisite for successful operative care. For different applications, diverse computer-assisted systems have been developed and clinically evaluated. This paper presents the implementation and evaluation of a new modular concept.

Are normal hips being labeled as pathologic? A CT-based method for defining normal acetabular coverage.

Background: Plain radiographic measures of the acetabulum may fail to accurately define coverage or pathomorphology such as impingement or dysplasia. CT scans might provide more precise measurements for overcoverage and undercoverage. However, a well-defined method for such CT-based measurements and normative data regarding CT-based acetabular coverage is lacking.

Immunoproteasomes shape the transcriptome and regulate the function of dendritic cells.

By regulating protein degradation, constitutive proteasomes (CPs) control practically all cellular functions. In addition to CPs, vertebrates express immunoproteasomes (IPs). The major nonredundant role ascribed to IPs is their enhanced ability to generate antigenic peptides.

A key role for EZH2 and associated genes in mouse and human adult T-cell acute leukemia.

In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2). Tumor cells show little residual H3K27 trimethylation marks compared with controls. EZH2 is a component of the PRC2 Polycomb group protein complex, which is associated with DNA methyltransferases.

Breast carcinoma-associated fibroblasts rarely contain p53 mutations or chromosomal aberrations.

It has become increasingly clear that the cells within the tumor microenvironment play a critical role in cancer growth and metastasis. Studies in experimental models suggest that carcinoma-associated fibroblasts (CAF) differ from normal fibroblasts and are capable of promoting cancer progression through a variety of mechanisms. At present, a definitive view is lacking on whether genomic abnormalities are present and whether they might underlie the observed phenotypic differences.

Laboratory and field cage studies on female-targeted attract-and-kill bait stations for Anastrepha suspensa (Diptera: Tephritidae).

Background: Development of attract-and-kill bait stations for pest fruit flies has been limited by the water solubility of sugar needed as a feeding stimulant and by the volatility of chemical attractants. A wax-based matrix was developed that provides the longevity needed for field use and is biodegradable.

Results: Laboratory bioassays with the Caribbean fruit fly, Anastrepha suspensa (Loew), confirmed the efficacy of bait stations containing avermectin, methomyl, spinosad and phloxine B.

New visualization tools: computer vision and ultrasound for MIS navigation.

Background: A versatile image acquisition method called echo surgetics has been developed for minimally invasive computer-assisted orthopaedic procedures. The principle of echo surgetics is to use freehand three-dimensional (3D) ultrasound to acquire relevant 3D bone surface and point data transcutaneously, eliminating access problems associated with conventional digitizers. The concept has been implemented in three technologies: Echo Point, Echo Matching and Echo Morphing.

Praxiteles: a miniature bone-mounted robot for minimal access total knee arthroplasty.

We have been working to develop a compact, accurate, safe, and easy-to-use surgical robot for minimally invasive total knee arthroplasty (TKA). The goal of our bone-mounted robot, named Praxiteles, is to precisely position a surgical bone-cutting guide in the appropriate planes surrounding the knee, so that the surgeon can perform the planar cuts manually using the guide. The robot architecture is comprised of 2 motorized degrees of freedom (DoF) whose axes of rotation are arranged in parallel, and are precisely aligned to the implant cutting planes with a 2 DoF adjustment mechanism.

Automated hydraulic tensor for Total Knee Arthroplasty.

To obtain a long lifespan of knee prosthesis, it is necessary to restore the alignment of the lower limb. In some cases of severe arthrosis, the ligament envelope of the joint may be deformed, inducing an asymmetric laxity once the lower limb is realigned. Because there is not yet unanimity regarding how to optimally measure or implement soft tissue balance, we provide a means to acquire a variety of measurements.

SURGETICA at Grenoble: from computer assisted medical interventions to quality inspired surgery.

Research on "Computer Assisted Medical Interventions" (CAMI) was initiated in Grenoble in 1984, as an attempt to take up the challenge of "Minimally Invasive Interventions", thanks to the introduction of Information and Communication Techniques in the Operating Room. In a first section, we will describe our initial vision. The corresponding achievements will then be presented.