Projection du fardeau du cancer au Canada en 2024.

CONTEXTE: Les données de surveillance du cancer sont essentielles pour mieux comprendre les lacunes et les progrès réalisés dans la lutte contre le cancer. Nous avons cherché à résumer les répercussions prévues du cancer au Canada en 2024, en effectuant des projections sur les nouveaux cas de cancer et les décès par cancer, par sexe et par province ou territoire, pour tous les âges confondus. MÉTHODES: Nous avons obtenu les données sur les nouveaux cas de cancer (c.-à-d., l'incidence, 1984­2019) et les décès par cancer (c.-à-d., la mortalité, 1984­2020) du Registre canadien du cancer et de la Base canadienne de données de l'état civil ­ Décès, respectivement. Nous avons projeté les chiffres et les taux d'incidence du cancer et de mortalité jusqu'en 2024 pour 23 types de cancer, par sexe et par province ou territoire. Nous avons calculé des taux normalisés selon l'âge au moyen de données de la population type canadienne de 2011. RÉSULTATS: En 2024, les nombres de nouveaux cas de cancer et de décès causés par le cancer devraient atteindre 247 100 et 88 100, respectivement. Le taux d'incidence normalisé selon l'âge (TINA) et le taux de mortalité normalisé selon l'âge (TMNA) devraient diminuer légèrement par rapport aux années précédentes, tant chez les hommes que chez les femmes, avec des taux plus élevés chez les hommes (TINA de 562,2 pour 100 000, et TMNA de 209,6 pour 100 000 chez les hommes; TINA de 495,9 pour 100 000 et TMNA de 152,8 pour 100 000 chez les femmes). Les TINA et les TMNA de plusieurs cancers courants devraient continuer à diminuer (p. ex., cancer du poumon, cancer colorectal et cancer de la prostate), tandis que ceux de plusieurs autres cancers devraient augmenter (p. ex., cancer du foie et des voies biliaires intrahépatiques, cancer du rein, mélanome et lymphome non hodgkinien). INTERPRÉTATION: Bien que l'incidence globale du cancer et la mortalité connexe sont en déclin, il devrait y avoir une augmentation des nouveaux cas et des décès au Canada en 2024, en grande partie en raison de la croissance et du vieillissement de la population. Les efforts en matière de prévention, de dépistage et de traitement ont atténué les répercussions de certains cancers, mais ces projections à court terme soulignent l'effet potentiel du cancer sur les gens et les systèmes de soins de santé au Canada.

Entering the Next Phase: Predicting Biological Effects of Biomolecular Condensates.

Biomolecular condensates are increasingly recognized as important drivers of cellular function; their dysregulation leads to pathology and disease. We discuss three questions in terms of the impending utility of data-driven techniques to predict condensate-driven biological outcomes, i.e., the impact of cellular state changes on condensates, the effect of condensates on biochemical processes within, and condensate properties that result in cellular dysregulation and disease.

Identification of hypermucoviscous Klebsiella pneumoniae K1, K2, K54 and K57 capsular serotypes by Raman spectroscopy.

Antimicrobial resistance poses a significant challenge in modern medicine, affecting public health. Klebsiella pneumoniae infections compound this issue due to their broad range of infections and the emergence of multiple antibiotic resistance mechanisms. Efficient detection of its capsular serotypes is crucial for immediate patient treatment, epidemiological tracking and outbreak containment. Current methods have limitations that can delay interventions and increase the risk of morbidity and mortality. Raman spectroscopy is a promising alternative to identify capsular serotypes in hypermucoviscous K. pneumoniae isolates. It provides rapid and in situ measurements with minimal sample preparation. Moreover, its combination with machine learning tools demonstrates high accuracy and reproducibility. This study analyzed the viability of combining Raman spectroscopy with one-dimensional convolutional neural networks (1-D CNN) to classify four capsular serotypes of hypermucoviscous K. pneumoniae: K1, K2, K54 and K57. Our approach involved identifying the most relevant Raman features for classification to prevent overfitting in the training models. Simplifying the dataset to essential information maintains accuracy and reduces computational costs and training time. Capsular serotypes were classified with 96 % accuracy using less than 30 Raman features out of 2400 contained in each spectrum. To validate our methodology, we expanded the dataset to include both hypermucoviscous and non-mucoid isolates and distinguished between them. This resulted in an accuracy rate of 94 %. The results obtained have significant potential for practical healthcare applications, especially for enabling the prompt prescription of the appropriate antibiotic treatment against infections.

Projected estimates of cancer in Canada in 2024.

BACKGROUND: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. METHODS: We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. RESULTS: In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). INTERPRETATION: Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.

Progress in cancer control leads to a substantial number of cancer deaths avoided in Canada.

It is currently not known how many more cancer deaths would have occurred among Canadians if cancer mortality rates were unchanged following various modern human interventions. The objective of this study was to estimate the number of cancer deaths that have been avoided in Canada since the age-standardized overall cancer mortality rate peaked in 1988. We applied the age-specific overall cancer mortality rates from 1988 to the Canadian population for all subsequent years to estimate the number of expected deaths. Avoided cancer deaths were estimated as the difference between the observed and expected number of cancer deaths for each year. Since 1988, there have been 372 584 (standardized mortality ratio = 0.77) and 120 045 (standardized mortality ratio = 0.90) avoided cancer deaths in males and females, respectively (492 629 total). Nearly half a million cancer deaths have been avoided in Canada since the overall cancer mortality rate peaked, which demonstrates the exceptional progress made in modern cancer control in Canada.

Detection of Water Contaminants by Organic Transistors as Gas Sensors in a Bottom-Gate/Bottom-Contact Cross-Linked Structure.

Detecting volatile organic compounds is a fundamental step in water quality analysis. Methylisoborneol (MIB) provides a lousy odor to water, whereas geosmin (GEO) is responsible for its sour taste. A widely-used technique for their detection is gas-phase chromatography. On the other hand, an electronic nose from organic thin-film transistors is a cheaper and faster alternative. Poly(2,5-bis(3-tetradecyl-thiophen-2-yl)thieno[3,2-b]thiophene) (PBTTT-C14) features semiconducting properties suitable for organic electronics. However, in order to expose the active layer in a bottom-gate transistor structure with photolithographically patterned electrodes, a cross-linked dielectric such as poly(4-vinyl phenol) (PVP) is necessary. In this work, the cross-linking was demonstrated using FTIR and Raman spectroscopies, as well as high-k capacitors with a dielectric constant of 5.3. The presence of enhanced crystallinity with terrace formation in the semiconducting film was confirmed with UV-visible spectrophotometry, atomic force microscopy, and X-ray diffraction. Finally, for the first time, a PBTTT-C14 transistor on cross-linked PVP was shown to respond to isoborneol with a sensitivity of up to 6% change in mobility per ppm. Due to its similarity to MIB, a system comprising these sensors must be investigated in the future as a tool for sanitation companies in real-time water quality monitoring.

Lifetime probability of developing cancer and dying from cancer in Canada, 1997 to 2020.

Background: The lifetime probabilities of developing (LPdev) cancer and dying (LPdying) from cancer are useful summary statistics that describe the impact of cancer within a population. This study aims to present detailed LPdev and LPdying for cancer by sex and cancer type and to describe changes in these lifetime probabilities over time among the Canadian population. Data and methods: Cancer incidence data (1997 to 2018) were obtained from the Canadian Cancer Registry. All-cause and cancer mortality data (1997 to 2020) were obtained from the Canadian Vital Statistics - Death Database. LPdev and LPdying were calculated using the DevCan software, and trends over time were estimated using Joinpoint. Results: The LPdev for all cancers combined was 44.3% in Canada in 2018, with all results excluding Quebec. At the age of 60, the conditional probability of developing cancer was very similar (44.0% for males and 38.2% for females). The LPdying was 22.5% among the Canadian population in 2020, while the probability of dying from cancer conditional on surviving until age 60 was 25.1% for males and 20.5% for females. Generally, males experienced higher LPdev and LPdying for most specific cancers compared with females. Interpretation: LPdev and LPdying for cancer mirror cancer incidence and mortality rates. Cancer-specific changes in these probabilities over time are indicative of the cancer trends resulting from cancer prevention, screening, detection, and treatment. These changes in LPdev and LPdying provide insight into the shifting landscape of the Canadian cancer burden.

In Vitro Transcription-Translation in an Artificial Biomolecular Condensate.

Biomolecular condensates are a promising platform for synthetic cell formation and constitute a potential missing link between the chemical and cellular stage of the origins of life. However, it has proven challenging to integrate complex reaction networks into biomolecular condensates, such as a cell-free in vitro transcription-translation (IVTT) system. Integrating IVTT into biomolecular condensates successfully is one precondition for condensation-based synthetic cell formation. Moreover, it would provide a proof of concept that biomolecular condensates are in principle compatible with the central dogma, one of the hallmarks of cellular life. Here, we have systemically investigated the compatibility of eight different (bio)molecular condensates with IVTT incorporation. Of these eight candidates, we have found that a green fluorescent protein-labeled, intrinsically disordered cationic protein (GFP-K72) and single-stranded DNA (ssDNA) can form biomolecular condensates that are compatible with up to µM fluorescent protein expression. This shows that biomolecular condensates can indeed integrate complex reaction networks, confirming their use as synthetic cell platforms and hinting at a possible role in the origin of life.

Crowding-induced phase separation and gelling by co-condensation of PEG in NPM1-rRNA condensates.

The crowdedness of the cell calls for adequate intracellular organization. Biomolecular condensates, formed by liquid-liquid phase separation of intrinsically disordered proteins and nucleic acids, are important organizers of cellular fluids. To underpin the molecular mechanisms of protein condensation, cell-free studies are often used where the role of crowding is not investigated in detail. Here, we investigate the effects of macromolecular crowding on the formation and material properties of a model heterotypic biomolecular condensate, consisting of nucleophosmin (NPM1) and ribosomal RNA (rRNA). We studied the effect of the macromolecular crowding agent poly(ethylene glycol) (PEG), which is often considered an inert crowding agent. We observed that PEG could induce both homotypic and heterotypic phase separation of NPM1 and NPM1-rRNA, respectively. Crowding increases the condensed concentration of NPM1 and decreases its equilibrium dilute phase concentration, although no significant change in the concentration of rRNA in the dilute phase was observed. Interestingly, the crowder itself is concentrated in the condensates, suggesting that co-condensation rather than excluded volume interactions underlie the enhanced phase separation by PEG. Fluorescence recovery after photobleaching measurements indicated that both NPM1 and rRNA become immobile at high PEG concentrations, indicative of a liquid-to-gel transition. Together, these results provide more insight into the role of synthetic crowding agents in phase separation and demonstrate that condensate properties determined in vitro depend strongly on the addition of crowding agents.