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CHO cell culture high productivity relies on optimized culture medium management under fed-batch or perfused chemostat strategies enabling high cell densities. In this work, a dynamic metabolic model for CHO cells was further developed, calibrated and challenged using datasets obtained under four different culture conditions, including two batch and two fed-batch cultures comparing two different culture media. The recombinant CHO-DXB11 cell line producing the EG2-hFc monoclonal antibody was studied. Quantification of extracellular substrates and metabolites concentration, viable cell density, monoclonal antibody concentration and intracellular concentration of metabolite intermediates of glycolysis, pentose-phosphate and TCA cycle, as well as of energetic nucleotides, were obtained for model calibration. Results suggest that a single model structure with a single set of kinetic parameter values is efficient at simulating viable cell behavior in all cases under study, estimating the time course of measured and non-measured intracellular and extracellular metabolites. Model simulations also allowed performing dynamic metabolic flux analysis, showing that the culture media and the fed-batch strategies tested had little impact on flux distribution. This work thus paves the way to an in silico platform allowing to assess the performance of different culture media and fed-batch strategies.

Background/Objective: Vaccines administered during early childhood rely on caregivers being aware, willing, and able to vaccinate their child. Postpartum depression (PPD) could adversely affect a parent’s ability to undertake such preventive care. This systematic review sought to examine the relationship between PPD and timely vaccination in children. Methods: We systematically searched eight databases (MEDLINE ALL, Embase, PsycINFO, CINAHL, LILACS, Web of Science, Sociological Abstracts, and Scopus) from database inception to September 2023. We also reviewed reference lists of included studies. We included primary studies that examined the association between PPD and child vaccination status between birth and 24 months. Two researchers independently extracted data and assessed study quality. Results: In total, 5504 records were screened for eligibility. Of the 50 articles included in full-text assessment, 12 met the eligibility criteria. Most studies (83%) were conducted in high-income countries, with a minority (17%) from lower-middle income countries (LMICs). The sample size of studies varied from <500 (33%) to >450,000 participants (17%). Overall, six studies (50%) found a relationship between maternal PPD and child vaccinations not completed on time, and six (50%) found no relationship. In most studies that were assessed to be of high-quality and found a relationship, the magnitude of the absolute risk was small. Conclusions: We detected significant heterogeneity among the included studies. Further high-quality research using standardized definitions is needed to determine whether parents with PPD may require tailored strategies and supports that consider their symptoms and specific barriers to vaccination.

Objectives. To estimate the alcohol-attributable fraction (AAF) for suicide in the United States. Methods. Using restricted-access data from the National Violent Death Reporting System for 2021, we estimated the sex-specific AAF for suicide, among those 15 years of age and older, by sociodemographic characteristics and suicide means. An alcohol-attributable suicide was defined as that for which the decedent had a blood alcohol concentration of 0.10 grams per deciliter or higher. Results. In 2021, the AAF for suicide for males (20.2%) was significantly higher than that for females (17.8%; P < .001). The AAF for suicide was higher for both males and females who used a firearm as the means of suicide (23.4% and 22.8%, respectively) compared with their counterparts who used other means (16.5% and 15.9%, respectively). Conclusions. Despite some variation, AAFs for suicide were consistently high, with about 1 in 5 suicides being attributable to alcohol use. Therefore, suicide prevention initiatives in the United States should also target excessive alcohol use. ( Am J Public Health. Published online ahead of print December 19, 2024:e1–e5. https://doi.org/10.2105/AJPH.2024.307910 )

Training Deep Learning (DL) models with missing labels is a challenge in diverse engineering applications. Missing value imputation methods have been proposed to try to address this problem, but their performance is affected with Massive Proportion of Missing Labels (MPML). This paper presents a approach for handling MPML in Multivariate Long-Term Time Series Forecasting. It is an two-step process where interpolation (using Gaussian Processes Regression (GPR) and domain knowledge from experts) and prediction model are separated to enable the integration of prior domain knowledge. First, a set of samples of the possible interpolation of the missing outputs are generated by the GPR based on the domain knowledge. Second, the observed input sensor data and interpolated labels from GPR are used to train the prediction model. We evaluated our approach with the development of a soft-sensor with one real datasets to forecast the biomass during recombinant adeno-associated virus (rAAV) production in bioreactors. Our experimental results demonstrate the potential of the approach through quantitative evaluation of the generated forecasts in a case that would be extremely difficult to train a DL model due to MPML.

The production of monoclonal antibody (mAb) by mammalian cell culture is now a well established technology, after decades of intensive research. Significant improvements have been achieved through experimentation at all bioreactor scales, mainly based on intuition, enabling current production bioprocesses reaching high productivity while maintaining high cell concentration for extended time. Indeed, a significant amount of work has been made studying and describing CHO cell metabolism, identifying metabolic traits associated to culture behaviour. Combining these knowledge on cell metabolism and from bioreactor cultures, it was possible to optimize culture media composition as well as bioreactor culture feeding strategies. However, bioprocess productivity and reproductivity level vary among biosystems. Indeed, an efficient analysis of cell metabolism and process optimization require tools that can be descriptive and predictive, proposing optimized solutions and analyzing experimental results . With that in mind, the present masters thesis’ aim was to propose a mathematical model that satisfies those criteria. A dynamic model of CHO cells metabolism is thus presented in this thesis, calibrated, analyzed and challenged with experimental data. The model, having as only input the culture initial conditions such as the extracellular and intracellular concentrations of nutrients and metabolites, simulates the concentration profiles of metabolites (intracellular and extracellular), cell growth, antibody production as well as metabolic flux dynamics. The model includes the kinetic description of the metabolic flux rates by equations derived from known biochemical mechanisms, and mass balances based on the stoichiometry of the cell's central carbon metabolism including glycolysis, TCA cycle, pentose phosphate pathway amino acid metabolism, mAb synthesis and energetic metabolism. The model presented here represents a further development from previous work on the modeling of another CHO cell line. It is specifically designed to simulate the effect of environmental disturbances such as variations of the initial medium compositions and of nutrients feeding strategies. In order to fine-tune the model structure as well as the values of the kinetic parameters, the model was calibrated on four different bioreactor cultures. Batch and fed-batch cultures were performed using two different media. A sensitivity analysis was performed on model parameters of which 20 were identified as the most sensitive ones, which values have been optimized to minimize the simulation error with respect to experimental data. This was also helpful to identify the metabolic pathways affected by the most sensitive parameters. The model parameter values optimization step was performed following various strategies: using experimental data of all cultures, and distinct data subsets such as batch or fed-batch cultures only, and for each culture media. Studying confidence intervals (95%) of model parameter values determined from each data sets, we show that a limited set of model parameters could describe CHO cultures irrespectively to the medium composition or the batch and fed-batch strategy. Similar conclusion can be drawn dividing the culture into exponential growth and plateau phases, estimating distinct parameter values in each phase, versus a model that simulates the entire culture without any parameters change. The resulting model was then used to perform a dynamic metabolic flux analysis, which revealed that the metabolism of the recombinant CHO cell line in this study is highly robust and highly regulated; the external perturbations having little effect on flux distribution. This work thus confirms the applicability of the dynamic model as an in silico platform to study different types of culture media and medium feeding strategies. The model could be used to help plan experiments or to optimize culture process.

Les échanges verticaux de traceurs entre la surface et l’intérieur de l’océan affectent les cycles biogéochimiques. Quand la couche de mélange n’est pas influencée par la convection, ces échanges sont principalement dus aux vitesses verticales au bas de la couche de mélange et plus profond, associées aux processus aux méso et subméso-échelles. Ces vitesses, souvent plus petites que 1 mm s-1, sont difficiles à mesurer directement. Deux modèles quasi-géostrophiques tridimensionnels ont récemment été développés pour estimer la circulation à partir d’observations instantanées faîtes en surface. Le modèle quasigéostrophique de surface (SQG) considère l’océan comme ayant une couche infiniment profonde d’une stratification constante. Il estime la circulation selon les anomalies de flottabilité ou de hauteur des eaux de surface. Le modèle quasi-géostrophique de couche de mélange (MLQG) considère l’océan comme ayant deux couches juxtaposées ayant chacune une stratification constante : une couche de mélange en surface d’une épaisseur finie et une couche intérieure d’une profondeur infinie. La circulation est inférée des anomalies de flottabilité et de hauteur des eaux de surface. Bien que le modèle SQG ait été testé sur des observations in situ, le modèle MLQG a seulement été testé sur des simulations numériques. Ici, nous testons les deux modèles contre des observations in situ durant un événement d’affaiblissement filamentaire d’eau dense dans l’estuaire maritime du Saint-Laurent. Les résultats montrent que les deux modèles donnent des résultats similaires pour estimer les vitesses horizontales. Par contre, aucun des modèles n’est capable de reproduire les gradients verticaux de vitesses verticales observés en surface.

The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa. Here, using murine models of prostate cancer, the authors show that reduced fecal microbiota alpha-diversity correlates with increased prostate tumor burden, and that Omega-3 prebiotic supplementation reduces prostate cancer up-grading associated with a reduction of gut Ruminococcaceae and fecal butyrate levels.

Shared decision making (SDM) is a process whereby decisions are made together by patients and/or families and clinicians. Nevertheless, few patients are aware of its proven benefits. This study investigated the feasibility, acceptability and impact of an intervention to raise public awareness of SDM in public libraries. A 1.5 hour interactive workshop to be presented in public libraries was co-designed with Quebec City public library network officials, a science communication specialist and physicians. A clinical topic of maximum reach was chosen: antibiotic overuse in treatment of acute respiratory tract infections. The workshop content was designed and a format, whereby a physician presents the information and the science communication specialist invites questions and participation, was devised. The event was advertised to the general public. An evaluation form was used to collect data on participants' sociodemographics, feasibility and acceptability components and assess a potential impact of the intervention. Facilitators held a post-workshop focus group to qualitatively assess feasibility, acceptability and impact. All 10 planned workshops were held. Out of 106 eligible public participants, 89 were included in the analysis. Most participants were women (77.6%), retired (46.1%) and over 45 (59.5%). Over 90% of participants considered the workshop content to be relevant, accessible, and clear. They reported substantial average knowledge gain about antibiotics (2.4, 95% Confidence Interval (CI): 2.0-2.8; P < .001) and about SDM (4.0, 95% CI: 3.4-4.5; P < .001). Self-reported knowledge gain about SDM was significantly higher than about antibiotics (4.0 versus 2.4; P < .001). Knowledge gain did not vary by sociodemographic characteristics. The focus group confirmed feasibility and suggested improvements. A public library intervention is feasible and effective way to increase public awareness of SDM and could be a new approach to implementing SDM by preparing potential patients to ask for it in the consulting room.

Background In the general population, a higher omega‐3 polyunsaturated fatty acids intake is associated with lower levels of several psychological symptoms, especially depression. However, the existing evidence in cancer is equivocal. Methods This phase IIB double‐blind, placebo‐controlled trial was aimed at comparing the effects of eicosapentaenoic acid monoacylglyceride (MAG‐EPA) supplementation and high oleic acid sunflower oil (HOSO; placebo) on depression levels (primary outcome) and other symptoms (anxiety, fear of cancer recurrence, fatigue, insomnia, perceived cognitive impairments; secondary outcomes). Participants, recruited in a prostate cancer clinic, were randomized to MAG‐EPA (3.75 g daily; n = 65) or HOSO (3.75 g daily; n = 65) for 1 year post‐radical prostatectomy (RP), starting 4–10 weeks before surgery. Patients completed self‐report scales at baseline (before RP) and 3, 6, 9, and 12 months after: Hospital Anxiety and Depression Scale (HADS), Fear of Cancer Recurrence Inventory (FCRI), Insomnia Severity Index (ISI), Fatigue Symptom Inventory (FSI), and Functional Assessment of Cancer Therapy—Cognitive Function (FACT‐Cog). Results Analyses showed significant reductions in HADS‐depression, HADS‐anxiety, FCRI, ISI, FSI‐number of days, and FACT‐Cog‐impact scores over time. A significant group‐by‐time interaction was obtained on FACT‐Cog‐Impact scores only; yet, the temporal change was significant in HOSO patients only. Conclusions Several symptoms significantly decreased over time, mainly within the first months of the study. However, MAG‐EPA did not produce greater reductions than HOSO. Omega‐3 supplementation does not seem to improve psychological symptoms of men treated with RP.

Background Prostate cancer is the most commonly diagnosed cancer in north-American men. Few dietary or lifestyle interventions have been tested to prevent prostate cancer progression. Omega-3 fatty acid supplementation represents a promising intervention for prostate cancer patients. The aim of the study is to evaluate the effects of long-chain omega-3 polyunsaturated fatty acids (LCn3), more precisely eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation, on prostate cancer proliferation, inflammation mediators and quality of life among men who will undergo radical prostatectomy. Methods/design We propose a phase IIb, randomized, double-blind placebo-controlled trial of MAG-EPA supplementation for 130 men who will undergo radical prostatectomy as treatment for a prostate cancer of Gleason score ≥ 7 in an academic cancer center in Quebec City. Participants will be randomized to 6 capsules of 625 mg of fish oil (MAG-EPA) per capsule containing 500 mg of EPA daily or to identically looking capsules of high oleic acid sunflower oil (HOSO) as placebo. The intervention begins 4 to 10 weeks prior to radical prostatectomy (baseline) and continues for one year after surgery. The primary endpoint is the proliferative index (Ki-67) measured in prostate cancer cells at radical prostatectomy. A secondary endpoint includes prostate tissue levels of inflammatory mediators (cytokines and proteins) at time of radical prostatectomy. Changes in blood levels of inflammatory mediators, relative to baseline levels, at time of radical prostatectomy and 12 months after radical prostatectomy will also be evaluated. Secondary endpoints also include important aspects of psychosocial functioning and quality of life such as depression, anxiety, sleep disturbances, fatigue, cognitive complaints and prostate cancer-specific quality of life domains. The changes in these outcomes, relative to baseline levels, will be evaluated at 3, 6, 9 and 12 months after radical prostatectomy. Discussion The results from this trial will provide crucial information to clarify the role of omega-3 supplementation on prostate cancer proliferation, inflammation and quality of life. Trial registration ClinicalTrials.gov Identifier: NCT02333435. Registered on December 17, 2014. Last updated September 6, 2016.