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Many drug candidates fail to complete the entire drug development process because of poor physicochemical properties. Solubility is an important physicochemical property which plays a vital role in various stages of drug discovery and development. Several methods have been proposed to enhance the solubility of drugs, and complex formation with cyclodextrins is among them. Beta-cyclodextrin (ßCD) is a common excipient for solubilization of drugs. The aim of this study is to develop the mechanistic QSPR models to predict the solubility enhancement of a drug in the presence of ßCD. In this study, the solubility enhancement of some drugs in the presence of 10mM ßCD at 25°C was experimentally determined or collected from the literature. Two different models to predict the solubilization by ßCD were developed by binary logistic regression using structural properties of drugs with more than 80% accuracy. Polar surface area and excess molar refraction are the main parameters for estimating solubilization by ßCD. Moreover, other descriptors related to hydrophobicity and the capability of hydrogen bonding formation of molecules could improve the accuracy of the established models.

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Individuals who maintain group memberships in their community tend to experience improved well-being relative to those who participate in few or no groups. There are, however, few investigations targeting variability in the correlates of group membership across the lifespan. The present examination probed age-related variability in the association between group memberships and subjective connectedness as well as well-being. Participants included 3,940 (mean age = 45.61 years, standard deviation [SD] = 15.62) Canadian and American respondents who completed an online survey during August of 2020 (i.e., amidst the COVID-19 pandemic). Time-varying effects modelling was used to estimate coefficients for group membership at each age within the sample. Memberships in social groups positively predicted connectedness, and this association was strongest in middle-to-older age; a similar association was also evident when predicting well-being. Connectedness was also a positive predictor of well-being throughout most ages. These findings build on emerging research conveying how group memberships have significance for people currently in middle-to-older age.

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Alternative methods to animal testing are used in fundamental and clinical research, for the realization of studies for regulatory purposes, and also screening operations in the development of new molecules. They are based on in vitro (cell models) or in silico (mathematical models) replacement methods. They have been largely promoted by the 3Rs rule (Replace, Reduce, Refine) which aims at regulating animal experimentation. For biomedical research, these different methods are valuable tools for better understanding the physiology of organisms and the mechanisms of the effects of chemicals and physical agents on them.

Title: Les méthodes alternatives à l'expérimentation animale, présent et futur. Abstract: Les méthodes alternatives à l'expérimentation animale sont utilisées en recherche fondamentale et clinique, pour la réalisation d'études à visée réglementaire et d'opérations de criblage en matière de développement de nouvelles molécules. Elles reposent sur des procédures de remplacement in vitro (modèles cellulaires) ou in silico (modèles mathématiques). Les méthodes alternatives ont été largement promues par la règle des 3R (Remplacer, Réduire, Raffiner) qui vise à encadrer l'expérimentation animale. Dans le domaine de la recherche, ces différentes méthodes sont des outils précieux qui permettent de mieux comprendre la physiologie des organismes et les mécanismes d'action des agents chimiques et physiques sur ces derniers.

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OBJECTIVES: The assessment of personality traits is most often based on self-report. However, a growing body of research has shown that informant-report is a valuable and too often overlooked source of unique information. The aim of this study was to validate the French version of the informant-report form of the Big Five Inventory-2 (BFI-2) which assesses 15 facet traits in addition to the five major trait domains. METHODS: We asked 699 psychology and sports science and technology students to describe a person they knew well using the BFI-2 and obtained 661 valid records with demographic information. The data were analyzed using a bi-factor exploratory structural equation model with five bifactors corresponding to the Big Five domains, and three group factors (facets) each. RESULTS: This model had an excellent overall fit. Cronbach's alpha coefficients for the five domains were very satisfactory and the McDonald's omega coefficients were even better. The scales that measured the five major factors were therefore highly reliable, although Extraversion was somewhat less so. The scales measuring facets all had high reliability as measures of the whole formed by the major factor and the group factor. In addition, ten of them were reliable measures of their specific factor, and the remaining five appeared to be pure measures of the five domains. CONCLUSIONS: The informant-report form of the BFI-2 is a reliable instrument which is easy and quick to administer. These qualities should enable clinicians and researchers to exploit the much-neglected source of original information provided by informant-reports.

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An experiment conducted with 'open microcosm' made by connected sedimentary compartments with different qualities was for 30 days to evaluate the migratory behaviour of nematodes as induced by exposure to pyrene. The nematofauna was collected along with sediment from a reference site in Bizerte lagoon. Following one week acclimatization period, the populated sediments were topped with azoic sediments, with a pyrene concentration of 150 µg kg-1. The concentration of pyrene from sediments was measured on a weekly basis. A stable status of nematode assemblages was reached between the upper and lower compartments in each microcosm, whatever the treatment type. An upward exploratory phase was observed during the first two weeks within the assemblages, possibly induced by the repellent chemodetection of pyrene. This observation was confirmed by the toxicokinetic properties and molecular interactions of pyrene with the germ-line development Protein 3 and sex-determining protein of Caenorhabditis elegans as nematode model.

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As the Recycling of wood waste becomes more important each year, wood products that contain urea-formaldehyde resins gained more attention due to the release of formaldehyde and other chemicals which have a critical impact on humans health and the environment. In this study, the hydrolysis of wood wastes from a French furniture industry was studied under different controlled conditions (temperature/pressure, steam ratio). An original on-line method to measure the emission of formaldehyde and ammonia using a FTIR spectrometer and a dilution system was applied successfully in this study. The effect of operatory conditions on formaldehyde and ammonia released is discussed. A mathematical model was also introduced to model the behavior of the ammonia and formaldehyde emission in the hydrolysis of wood waste.

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Following the market trends, the consumption of fresh and cold-pressed juice in Europe is increasing. However, a primary concern - particularly in apple juice - is the related outbreaks caused by food-borne pathogens. One of the challenges is to find methods able to reduce pathogenic loads while avoiding deterioration of nutritional properties and bioactive compounds that occur in thermal pasteurization processes. In this study, the inactivation of Escherichia coli, Salmonella enterica and Listeria monocytogenes was evaluated under different ultraviolet C (UVC254nm) light treatments (up to 10,665.9 ± 28.1 mJ/cm2), in two different steps of the production chain (before and after juice processing): on apple peel discs and in apple juice. The systems proposed were a horizontal chamber with UVC254nm emitting lamps treating the product disposed at a distance of 12 cm, and a tank containing UVC254nm lamps and in which the product is immersed and agitated. Final reductions ranged from 3.3 ± 0.5 to 5.3 ± 0.4 logarithmic units, depending on the microorganism, matrix and used device. The survival curves were adjusted to Weibull and biphasic models (R2-adj ≥ 0.852), and UVC doses needed for the first decimal reduction were calculated, being lower for the apple peel discs (0.20 to 83.83 mJ/cm2) than they were for apple juice (174.60 to 1273.31 mJ/cm2), probably for the low transmittance of the apple juice compared to the surface treatment occurring on the peels. Within the treatments evaluated, the UVC254nm irradiation of apple peels immersed in water was the best option as it resulted in a reduction of the tested microorganisms of ca. 2-3 log units at lower UVC254nm doses (< 500 mJ/cm2) when compared to those occurring in apple peel treated with the UVC chamber and in juice. As contamination can proceed from apples, the sanitization of these fruit prior to juice production may be helpful in reducing the safety risks of the final product, reducing the drawbacks related to the poor transmittance of the fruit juices.

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OBJECTIVES: The resection of malignant bone tumors of the pelvis causes significant loss of substances making covering procedures difficult. The gluteus maximus pedicled flap allows some reconstructions, but its use in vascular sacrifice is not clearly established. The objective of our study was to study its vascularization in order to assess the possibility of vascular sacrifice during carcinological resection of a pelvic tumor. METHOD: We first performed a vascular mapping of the gluteus maximus muscle using 3-dimensional (3D) models from CT angiography in patients with Leriche syndrome. These models were compared to a cadaveric dissection of 2 injected muscles. A second 3D modeling from postoperative scans was performed in patients who had a gluteus maximus flap after pelvic carcinological surgery. RESULTS: Ten patients with Leriche syndrome had a 3D model from their scanners. Three distinct arterial systems were identified. Seven patients had a flap from the gluteus maximus muscle, including 3 cases of an Inverted pedicled Hemi Gluteus maximus flap (HGI). According to the modeling, the richness of the vascular network would allow the sacrifice of the superior gluteal pedicle without compromising the viability of this flap. CONCLUSION: Our study made it possible to confirm the richness of the vascular network of the gluteus maximus muscle and to consider the theoretical possibility of sacrificing the superior gluteal pedicle without endangering an HGI pedicled muscle flap.

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Three-dimensional (3D) culture of organoids from primary cells (wild type) or tumoroids from tumor cells, is used to study the physiological mechanisms in vivo, in order to model normal or tumor tissues more accurately than conventional two-dimensional (2D) culture. The features of this 3D culture, such as the three-dimensional structure, the self-renewal capacity and differentiation are preserved and appropriate to cancer study since their cellular characteristics are very similar to in vivo models. Here, we summarize the recent advances in the rapidly evolving field of organoids and their applications to cancer biology, clinical research and personalized medicine.

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BACKGROUND: One diagnosis of cystic fibrosis involves measuring the nasal transepithelial potential difference (NPD) as a complementary technique in the forms of the disease, where the sweat test is non-discriminating. The NPD is measured using solutions with and without chlorides, containing a variety of substances whose activities on nasal mucus membranes are studied or assessed. Among the solutions described in the literature and used in specialized centers, none seems to be best adapted for industrial production for reasons of stability (formulas of the international consensus of Rowe et al. and formulas of Knowles et al.) and/or potential toxicity (formulas of Middleton et al.). OBJECTIVE(S): Defining new formulas, according to those of the international consensus, with greater physicochemical and microbiological stability. METHODS: The reformulation tests were conducted on the formulas of Rowe et al., using CHESS® (CHemical Equilibrium of Species and Surfaces) software for modeling aqueous systems that substantially reduced the number of experiments. CHESS® software was first validated using models of ideal and non-ideal solutions. Thereafter, experimentation was carried out for the sake of comparison with theoretical data. RESULTS: CHESS® software using models of ideal and non-ideal solutions were validated. The experimentation confirmed the theoretical data, and new formulas were assessed based on their physicochemical (pH, content, Osmolality) and microbiological stability. CONCLUSION: The new formulas defined here guarantee excellent physicochemical and microbiological stability of diagnostic solutions, indispensable criteria for harmonizing and comparing results from different specialized centers using NPD measurements. These new formulas apply to the harmonization approach of techniques for measuring the nasal transepithelial potential difference.

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A multi-stage sampling strategy selected 1387 on-reserve First Nations adults in Ontario. Foods from a 24-hour dietary recall were assigned to the 100 most common food groups for men and women. Nutrients from market foods (MF) and traditional foods (TF) harvested from the wild as well as MF costs were assigned based on the proportions of total grams consumed. Linear programming was performed imposing various constraints to determine whether it was possible to develop diets that included the most popular foods while meeting Institute of Medicine guidelines. Final models were obtained for both sexes with the top 100 food groups consumed while limiting the nutrient-poor foods to no more than the actual observed intake. These models met all nutrient constraints for men but those for dietary fibre, linoleic acid, phosphorus, and potassium were removed for women. MF costs were obtained from community retailers and online resources. A grocery list was then developed and MF were costed for a family of 4. The grocery list underestimated the actual weekly food cost because TF was not included. Contemporary observed diets deviated from healthier historic First Nations diets. A culturally appropriate diet would include more traditional First Nations foods and fewer MF. Novelty: Linear programming is a mathematical approach to evaluating the diets of First Nations. The grocery list is representative of food patterns within Ontario First Nations and can be used as an alternative to the nutritious food basket used for public health food costing.

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Hyaluronic acid is a high-molecular-weight polysaccharide that is widely distributed in animal tissues. Bacterial hyaluronidases degrade hyaluronic acid as secreted enzymes and have been shown to contribute to infection. Staphylococcus aureus UAMS-1 is a clinical isolate that codes for two hyaluronidases (hysA1 and hysA2). Previous research has shown the presence of a full-length HysA1 protein from the S. aureus UAMS-1 strain with no evidence of enzymatic activity. In this study, the coding and upstream promoter regions of hysA1 from the S. aureus UAMS-1 strain were cloned, sequenced, and compared to the hysA1 gene from the S. aureus Sanger 252 strain. A single base change resulting in an E480G amino acid change was identified in the hysA1 gene from the S. aureus UAMS-1 strain when compared to the hysA1 gene from S. aureus Sanger 252. A plasmid copy of hysA1 from S. aureus Sanger 252 transduced into an S. aureus UAMS-1 hysA2 deletion mutant strain restored near wild-type levels of enzymatic activity. Homology modeling of the HysA1 hyaluronidase was performed with SWISS-MODEL using hyaluronidase from Streptococcus pneumoniae as the template, followed by a series of structural analyses using PyMOL, PLIP, PDBsum, and HOPE servers. This glutamic acid is highly conserved among hyaluronidases from Staphylococcus and other gram-positive bacteria. A series of structural analyses suggested that Glu-480 in HysA1 is critically responsible for maintaining the structural and functional ensemble of the catalytic and tunnel-forming residues, which are essential for enzyme activity. The missense mutation of Glu-480 to Gly introduces a loss of side chain hydrogen bond interactions with key residues Arg-360 and Arg-364, which are responsible for the tunnel topology, resulting in displacement of the substrate from an ideal position for catalysis through a localized conformational change of the active site. There is a high degree of relatedness among several gram-positive bacterial hyaluronidases; the loss of enzymatic activity of HysA1 in the S. aureus UAMS-1 strain is most likely caused by the mutation identified in our study. The role of hyaluronidase in staphylococcal infection and the redundancy of this gene are yet to be determined.

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INTRODUCTION: Over the past few years, 3D printing has evolved rapidly. This has resulted in an increasing number of scientific publications reporting on the medical use of 3D printing. These applications can range from patient information, preoperative planning, education, or 3D printing of patient-specific surgical implants. The objective of this review was to give an overview of the different applications in urology and other disciplines based on a selection of publications. METHODS: In the current narrative review the Medline database was searched to identify all the related reports discussing the use of 3D printing in the medical field and more specifically in Urology. 3D printing applications were categorized so they could be searched more thoroughly within the Medline database. RESULTS: Three-dimensional printing can help improve pre-operative patient information, anatomy and medical trainee education. The 3D printed models may assist the surgeon in preoperative planning or become patient-specific surgical simulation models. In urology, kidney cancer surgery is the most concerned by 3D printing-related publications, for preoperative planning, but also for surgical simulation and surgical training. CONCLUSION: 3D printing has already proven useful in many medical applications, including urology, for patient information, education, pre-operative planning and surgical simulation. All areas of urology are involved and represented in the literature. Larger randomized controlled studies will certainly allow 3D printing to benefit patients in routine clinical practice.

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Fractures of the hamate are rare, and a clear treatment algorithm does not exist. Nonetheless, surgical treatment is generally recommended for displaced fractures using a dorsal approach. There is also a lack of data on hamate malunion. We present a case of a 28-year-old female with a coronal malunion of the hamate and hamate hook fracture. Because the triquetrum prevented direct access to the fracture, we planned and undertook a transtriquetral coronal osteotomy based on three-dimensional computed tomography imaging data. After removing the bone callus, reduction was possible with subsequent fixation. We recommend performing a transtriquetral osteotomy to treat an otherwise inaccessible fracture or malunion of select hamate fractures.

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Sport climbing is increasingly popular and consultations by climbers in hand surgery departments are on the increase. The pathologies related to this sport concern essentially the pulley system, tendons being rarely affected. We report the case of a male climber who presented an atypical rupture of the flexor superficialis tendon in his left middle finger sustained when using an atypical climbing grip technique: the "hook grip". This consists in extension of the metacarpophalangeal joints and maximal flexion of the proximal interphalangeal joints with force exerted only on middle phalanx of the middle finger. A biomechanical analysis using finger musculoskeletal modeling was performed to compare the hook grip to other grips, and the patient's recovery performance was assessed. Adapted functional treatment with physiotherapy seems to have been a good option for the treatment of this atypical lesion since the patient recovered normal use of his finger in daily life. He recovered maximal force in climbing holds. The biomechanical analysis confirmed that the atypical "hook grip" was likely at the origin of the rupture, since flexor digitorum superficialis tendon force for this grip is greater than in other climbing grip techniques. The "hook grip" seems to be dangerous and should be used cautiously by climbers to prevent similar pathology. Additionally, the patient should henceforth be careful when climbing, since the biomechanical model showed that the remaining flexor digitorum profundus tendon was overused.

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Parameters extraction is instrumental to standard PV cells design. Reports indicates that heuristic algorithms are the most effective methods for accurately determinining the values of parameters. However, local concentration is against recent heuristic methods, and they are inhibited producing optimal results. This paper seeks to show that combining the heuristics algorithms with the Newton Raphson method can considerably increased the accuracy of results. An inspired artifact technique from the drone squadron simulation from control center is proposed for the extraction of the best constitutive parameters. This study equally provides clarifications on the approaches recently reported and proposed to build objective function. Furthermore, comparative evaluation of the current ten best heuristics algorithms that are published in the PV estimation domain is also undertaken. Moreover, this study investigates the convergence of algorithms when points of the number of current-voltage characteristics are varied. The results from this study highlight the differences between the two formulation, and it shows the best formulation accuracy. The results obtained from seven study cases that are considered in this present study, with the combined Newton Raphson performance method and Drone Squadron optimisation, were employed to extract precise PV module parameters.The study of the numbers of points reveals that the algorithm converges and is more precise when the numbers of points of the I-V characteristic are reduced. However, if these points are minimal, the algorithm will be hindered from returning optimal results.

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The Sustainable Development Goals (SDGs) encourage nations to substantially increase food production to achieve zero hunger (SDG 2) while preserving life on land (SDG 15). A key question is how to reconcile these potentially competing goals spatially. We use integer linear programming to develop an 'integrated land use planning framework' that identifies the optimal allocation of 17 crops under different hypothetical conservation targets while meeting agricultural demands by 2030. Intensifying existing cropland to maximum yield before allocating new cropland would reduce land requirement by 43% versus cropland expansion without intensification. Even with yield gap closure, tropical and sub-tropical crops still require expansion, primarily allocated to Venezuela, eastern Brazil, Congo Basin, Myanmar and Indonesia. Enforcement of protected areas, via avoiding conversion in 75% of Key Biodiversity Areas and 65% of intact areas, is vital to attain biodiversity targets but bears large opportunity costs, with agricultural rents dropping from $4.1 to $2.8 trillion. Although nationally constrained forest conservation efforts would earn 9% less agricultural rents compared to globally coordinated conservation solutions, they were also able to reduce intact habitat and forest loss (43% and 35% reduction). Our results demonstrate that careful choice of the allocation of future cropland expansion, could dramatically reduce-but not eliminate-the tradeoffs between the SDGs for food production and land biodiversity conservation.

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BACKGROUND: Whole-body vibration is a major cause of lower back pain among employees, and the medical and preventive care teams of occupational health departments are often confronted with lower back pain problems among machine operators. OBJECTIVES: The objectives of this research are to determine the number of excavator drivers exposed to whole-body vibration levels above 0.5m/s2, identify other exposure factors that may contribute to back pain, and propose corrective measures. METHODS: Vibration measurements were carried out on individual excavator drivers while they were observed carrying out working tasks, after which prevention advice is given. Factors which determine vibration levels are logged on to a database. RESULTS: The multivariate analysis of several determining factors shows vibration exposure levels vary depending on the varied work tasks being carried out. CONCLUSION: This study identifies exposed employees among excavator operators. For each workstation, the determining factors that could explain the high exposures to vibrations are identified. This work shows the important role of tasks on exposure levels. A better adaptation of the tools used to carry out work tasks would allow a decrease in the vibration level of this type of machine.

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Adolescents often report low moderate-to-vigorous physical activity (MVPA) and high screen time. We modeled sex-specific MVPA and screen time trajectories during adolescence and identified contemporaneous patterns of evolution. Data were drawn from 2 longitudinal investigations. The Nicotine Dependence in Teens (NDIT) study included 1294 adolescents recruited at age 12-13 years who completed questionnaires every 3 months for 5 years. The Monitoring Activities of Teenagers to Comprehend their Habits (MATCH) study included 937 participants recruited at age 9-12 years who completed questionnaires every 4 months for 7 years. MVPA was measured as the number of days per week of being active for at least 5 min (NDIT) or 60 min (MATCH). In both studies, screen time was measured as the number of hours spent weekly in screen activities. In each study, sex-specific group-based trajectories were modeled separately for MVPA and screen time from grade 7 to 11. Contemporaneous patterns of evolution were examined in mosaic plots. In both studies, 5 MVPA trajectories were identified in both sexes, and 4 and 5 screen time trajectories were identified in boys and girls, respectively. All combinations of MVPA and screen time trajectories were observed. However, the contemporaneous patterns of evolution were favourable in 14%-31% of participants (i.e., they were members of the stable high MVPA and the lower screen time trajectories). Novelty: MVPA and screen time trajectories during adolescence and their combinations showed wide variability in 2 Canadian studies. Up to 31% of participants showed favourable contemporaneous patterns of evolution in MVPA and screen time. Using uniform methods for trajectory modeling may increase the potential for replication across studies.

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Our work has been carried out with the aim of providing a solution to decision-making problems encountered in information systems for supply chains in crisis situation. The supply chain represents a competitive advantage that companies seek to perpetuate. It aims to optimize the exchanges, or flows, that the company maintains with its suppliers and its customers. These flows can be of various natures. It can be information flows relating to supplies or product design, financial flows linked to purchases, or even flows of goods. The crisis management logistics is getting more and more attention, especially in the current context of the COVID-19 pandemic. For these systems, where it is never very easy to anticipate the evolution of the environment, the forms of changes undergone are varied and rapid. We aim to provide an answer to these challenges, in an approach that links optimization methods to the paradigm of artificial intelligence. We therefore propose to find mathematical models, and inter-agent cooperation protocols, to minimize the risk of stock shortage in any area of ​​the supply chain.