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.

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.

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.

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.

Automatic classification of Candida species using Raman spectroscopy and machine learning.

One of the problems that most affect hospitals is infections by pathogenic microorganisms. Rapid identification and adequate, timely treatment can avoid fatal consequences and the development of antibiotic resistance, so it is crucial to use fast, reliable, and not too laborious techniques to obtain quick results. Raman spectroscopy has proven to be a powerful tool for molecular analysis, meeting these requirements better than traditional techniques. In this work, we have used Raman spectroscopy combined with machine learning algorithms to explore the automatic identification of eleven species of the genus Candida, the most common cause of fungal infections worldwide. The Raman spectra were obtained from more than 220 different measurements of dried drops from pure cultures of each Candida species using a Raman Confocal Microscope with a 532 nm laser excitation source. After developing a spectral preprocessing methodology, a study of the quality and variability of the measured spectra at the isolate and species level, and the spectral features contributing to inter-class variations, showed the potential to discriminate between those pathogenic yeasts. Several machine learning and deep learning algorithms were trained using hyperparameter optimization techniques to find the best possible classifier for this spectral data, in terms of accuracy and lowest possible overfitting. We found that a one-dimensional Convolutional Neural Network (1-D CNN) could achieve above 80 % overall accuracy for the eleven classes spectral dataset, with good generalization capabilities.

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.

Incidence, Severity and Clinical Factors Associated with Hypotension in Patients Admitted to an Intensive Care Unit: A Prospective Observational Study.

Background: The majority of patients admitted to the intensive care unit (ICU) experience severe hypotension which is associated with increased morbidity and mortality. At present, prospective studies examining the incidence and severity of hypotension using continuous waveforms are missing. Methods: This study is a prospective observational cohort study in a mixed surgical and non-surgical ICU population. All patients over 18 years were included and continuous arterial pressure waveforms data were collected. Mean arterial pressure (MAP) below 65 mmHg for at least 10 s was defined as hypotension and a MAP below 45 mmHg as severe hypotension. The primary outcome was the incidence of hypotension. Secondary outcomes were the severity of hypotension expressed in time-weighted average (TWA), factors associated with hypotension, the number and duration of hypotensive events. Results: 499 patients were included. The incidence of hypotension (MAP < 65 mmHg) was 75% (376 out of 499) and 9% (46 out of 499) experienced severe hypotension. Median TWA was 0.3 mmHg [0−1.0]. Associated clinical factors were age, male sex, BMI and cardiogenic shock. There were 5 (1−12) events per patients with a median of 52 min (5−170). Conclusions: In a mixed surgical and non-surgical ICU population the incidence of hypotension is remarkably high.

Prevalence and Population Diversity of Listeria monocytogenes Isolated from Dairy Cattle Farms in the Cantabria Region of Spain.

Listeria monocytogenes is an opportunistic pathogen that is widely distributed in the environment. Here we show the prevalence and transmission of L. monocytogenes in dairy farms in the Cantabria region, on the northern coast of Spain. A total of 424 samples was collected from 14 dairy farms (5 organic and 9 conventional) and 211 L. monocytogenes isolates were recovered following conventional microbiological methods. There were no statistically significant differences in antimicrobial resistance ratios between organic and conventional farms. A clonal relationship among the isolates was assessed by pulsed field gel electrophoresis (PFGE) analysis and 64 different pulsotypes were obtained. Most isolates (89%, n = 187) were classified as PCR serogroup IVb by using a multiplex PCR assay. In this case, 45 isolates of PCR serogroup IVb were whole genome-sequenced to perform a further analysis at genomic level. In silico MLST analysis showed the presence of 12 sequence types (ST), of which ST1, ST54 and ST666 were the most common. Our data indicate that the environment of cattle farms retains a high incidence of L. monocytogenes, including subtypes involved in human listeriosis reports and outbreaks. This pathogen is shed in the feces and could easily colonize dairy products, as a result of fecal contamination. Effective herd and manure management are needed in order to prevent possible outbreaks.

ATP:Mg2+ shapes material properties of protein-RNA condensates and their partitioning of clients.

Many cellular condensates are heterotypic mixtures of proteins and RNA formed in complex environments. Magnesium ions (Mg2+) and ATP can impact RNA folding, and local intracellular levels of these factors can vary significantly. However, the effect of ATP:Mg2+ on the material properties of protein-RNA condensates is largely unknown. Here, we use an in vitro condensate model of nucleoli, made from nucleophosmin 1 (NPM1) proteins and ribosomal RNA (rRNA), to study the effect of ATP:Mg2+. While NPM1 dynamics remain unchanged at increasing Mg2+ concentrations, the internal RNA dynamics dramatically slowed until a critical point, where gel-like states appeared, suggesting the RNA component alone forms a viscoelastic network that undergoes maturation driven by weak multivalent interactions. ATP reverses this arrest and liquefies the gel-like structures. ATP:Mg2+ also influenced the NPM1-rRNA composition of condensates and enhanced the partitioning of two clients: an arginine-rich peptide and a small nuclear RNA. By contrast, larger ribosome partitioning shows dependence on ATP:Mg2+ and can become reversibly trapped around NPM1-rRNA condensates. Lastly, we show that dissipative enzymatic reactions that deplete ATP can be used to control the shape, composition, and function of condensates. Our results illustrate how intracellular environments may regulate the state and client partitioning of RNA-containing condensates.

Update on cancer incidence trends in Canada, 1984 to 2017. / Le point sur les tendances de l'incidence du cancer au Canada (1984-2017).

This paper highlights findings on cancer trends from the Canadian Cancer Statistics 2021 report. Trends were measured using annual percent change (APC) of age-standardized incidence rates. Overall, cancer incidence rates are declining (-1.1%) but the findings are specific to the type of cancer and patient sex. For example, in males, the largest decreases per year were for prostate (-4.4%), colorectal (-4.3%), lung (-3.8%), leukemia (-2.6%) and thyroid (-2.4%) cancers. In females, the largest decreases were for thyroid (-5.4%), colorectal (-3.4%) and ovarian (-3.1%) cancers.

Overall, cancer incidence is declining at a rate of −1.1% per year. In males, the two largest decreases were for prostate (−4.4% per year) and colorectal (−4.3% per year) cancer. In females, they were for thyroid (−5.4% per year) and colorectal (−3.4% per year) cancer. Melanoma (males: 2.2% per year; females: 2.0% per year) and multiple myeloma (males: 2.5% per year; females: 1.6% per year) rates are increasing. Cancer trends in Canada are dynamic and type-specific. The decreases for prostate and thyroid cancer underscore the importance of updating testing practices based on best evidence.

Dans l'ensemble, l'incidence du cancer diminue à un taux de −1,1 % par année. Les deux plus fortes baisses ont été observées chez les hommes pour le cancer de la prostate (−4,4 % par année) et le cancer colorectal (−4,3 % par année) et, chez les femmes, pour le cancer de la thyroïde (−5,4 % par année) et le cancer colorectal (−3,4 % par année). Les taux de mélanome sont en hausse (hommes : 2,2 % par année; femmes : 2,0 % par année) ainsi que ceux de myélome multiple (hommes : 2,5 % par année; femmes : 1,6 % par année). Les tendances en matière de cancer au Canada sont dynamiques et elles dépendent de chaque type de cancer. La diminution de l'incidence du cancer de la prostate et du cancer de la thyroïde souligne l'importance de mettre à jour les pratiques de dépistage à partir des meilleures données probantes.

Projected estimates of cancer in Canada in 2022.

BACKGROUND: Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022. METHODS: We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2018). Mortality data (1984-2019) were obtained from the Canadian Vital Statistics - Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population. RESULTS: An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces. INTERPRETATION: Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.

The interest of 100 versus 200 Hz tetanic stimulations to quantify low levels of residual neuromuscular blockade with mechanomyography: a pilot study.

A more sensitive method than the train-of-four ratio seems required to detect low levels of residual neuromuscular blockade before tracheal extubation. The goal of the study was to determine the potential benefit of 5 s of 100 versus 200 Hz tetanic stimulation to quantify the residual block with mechanomyography in anesthetised patients. Twenty informed and consenting 18- to 80-year-old patients undergoing nose surgery were included. On the left hand, neuromuscular transmission was continuously monitored by acceleromyography. On the right side, a new mecanomyographic device (Isometric Thumb Force©) recorded the force of thumb adduction (N) developed during 5 s of 100- and 200 Hz tetanic stimulations of the ulnar nerve at three consecutive times: baseline before inducing the neuromuscular blockade, at the time of contralateral train-of-four ratio 0.9 recovery, and 3 min after additional sugammadex reversal. Tetanic Fade Ratios (TFR = F residual/F max) were compared between 100 and 200 Hz stimulations using Student's t test. At the time of TOF ratio 0.9 recovery, both 100 and 200 Hz TFR were significantly decreased compared to baseline (0.61 and 0.16 on average, respectively, p < 0.0001). The 200 Hz TFR was significantly lower than the 100 Hz TFR (p < 0.0001). There were no differences between baseline and post-reversal TFR. The 200 Hz TFR has the potential to better describe low levels of residual neuromuscular blockade than the TOF ratio and 100 Hz TFR and would benefit from further investigations. Retrospectively registered in the Australian and New Zealand Clinical Trials Registry ACTRN12619000273189.

100 Hz-5 s tetanic stimulation to illustrate the presence of "residual paralysis" co-existing with accelerometric 0.90 train-of-four ratio-A proof-of-concept study.

BACKGROUND: An acceleromyographic train-of-four (TOF) ratio of 0.90 at extubation does not prevent postoperative pulmonary complications in surgical patients receiving non-depolarising muscle relaxants. This recent observation suggests that a more selective neuromuscular transmission monitoring parameter is mandatory to detect more precisely any remaining residual paralysis. The aim of our proof-of-concept study was to evaluate, in patients receiving rocuronium, the degree of 100-Hz, 5-s tetanic fade present when the acceleromyographic TOF ratio has recovered to 0.90. METHODS: Twenty adult patients scheduled for surgery under general anaesthesia were included. Before anaesthesia induction, a TOF-Watch SX™ and a VISUAL-ITF© (a prototype monitor for recording isometric force) were positioned on both hands. After induction but before rocuronium injection, a 100-Hz, 5-s tetanus (TET0) was delivered to both ulnar nerves. Thereafter, TOF stimulations every 15 s were delivered to both arms until a TOF ratio > 0.90 was recorded; then, a 100-Hz, 5-s tetanus (TET1) was recorded on the VISUAL-ITF© monitor. The values of the tetanic parameters (force) recorded at TET0 and TET1 were compared using a Wilcoxon rank sum test. RESULTS: Compared to TET0, tetanic parameters of TET1 were significantly lower (median [range]): maximal force 36.4 [19.2-82.6] vs. 25.5 [5.0-42.4] Newton (p < 0.005); residual force 36.2 [18.2-82.0] vs. 5.5 [0.20-38.3] Newton (p < 0.0001) and residual force/maximal force ratio 0.98 [0.89-0.99] vs. 0.17 [0.03-0.90] (p < 0.0001). CONCLUSION: Our results confirm that even when the acceleromyographic TOF ratios have recovered to above 0.90, the contralateral 100-Hz, 5-s tetanic stimulus may show tetanic fade characteristic of residual neuromuscular block, and may help improve the safety of tracheal extubation.

Active coacervate droplets are protocells that grow and resist Ostwald ripening.

Active coacervate droplets are liquid condensates coupled to a chemical reaction that turns over their components, keeping the droplets out of equilibrium. This turnover can be used to drive active processes such as growth, and provide an insight into the chemical requirements underlying (proto)cellular behaviour. Moreover, controlled growth is a key requirement to achieve population fitness and survival. Here we present a minimal, nucleotide-based coacervate model for active droplets, and report three key findings that make these droplets into evolvable protocells. First, we show that coacervate droplets form and grow by the fuel-driven synthesis of new coacervate material. Second, we find that these droplets do not undergo Ostwald ripening, which we attribute to the attractive electrostatic interactions and translational entropy within complex coacervates, active or passive. Finally, we show that the droplet growth rate reflects experimental conditions such as substrate, enzyme and protein concentration, and that a different droplet composition (addition of RNA) leads to altered growth rates and droplet fitness. These findings together make active coacervate droplets a powerful platform to mimic cellular growth at a single-droplet level, and to study fitness at a population level.

Inhibitory effects of Tomivosertib in acute myeloid leukemia.

The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for acute myeloid leukemia (AML). We evaluated the therapeutic potential of the highly-selective MNK1/2 inhibitor Tomivosertib on AML cells. Tomivosertib was highly effective at blocking eIF4E phosphorylation on serine 209 in AML cells. Such inhibitory effects correlated with dose-dependent suppression of cellular viability and leukemic progenitor colony formation. Moreover, combination of Tomivosertib and Venetoclax resulted in synergistic anti-leukemic responses in AML cell lines. Mass spectrometry studies identified novel putative MNK1/2 interactors, while in parallel studies we demonstrated that MNK2 - RAPTOR - mTOR complexes are not disrupted by Tomivosertib. Overall, these findings demonstrate that Tomivosertib exhibits potent anti-leukemic properties on AML cells and support the development of clinical translational efforts involving the use of this drug, alone or in combination with other therapies for the treatment of AML.