Research procedure acceptability through women during pregnancy and postpartum: A pilot study.

OBJECTIVE: To assess the feasibility and relevancy of a systematic data collection process in characterizing factors influencing research acceptability through women during pregnancy and early postpartum. METHODS: A pilot prospective observational crossover unicentric study was conducted in Est France. All the women (except language barrier and intensive care transfer) were called upon to complete a survey (33 questions). The primary endpoints were the participation rate and the completeness of the information. The secondary endpoint was the participants' sociodemographic background and preferences regarding research (bivariate analysis, P value <0.20). RESULTS: Within the research period (February 23-March 8, 114 childbirths), 105 women fitting the criteria were called upon for the survey. The participation rate and completeness were high. The participation rate was 93% with six lost to follow-up, and one refusal. The global filling rate was 95%. We highlighted two plausible variables of interests for research participation: women age older (P value 0.119) and level of education (P value 0.176). A sufficient cooling-off period, the commitment of women's health providers, and the possibility to accede research results might favor women's involvement. Acceptability would appear to be decreasing when the protocol implied fetal or neonatal data collection (compared to maternal data), unless research led to a better therapeutic option. CONCLUSION: The data collection process is highly feasible and provide consistent data. Larger-scale output obtention should enhance the conception and rollout of projects, first by calculating sample size based on potentials for recruitments adjusted to populations, characteristics and second by fitting the experimental design to women's expectations.

Assessing without harvesting: Pros and cons of environmental DNA sampling and image analysis for marine biodiversity evaluation.

Marine stock assessments or biodiversity monitoring studies, which historically relied on extractive techniques (e.g., trawl or grab surveys), are being progressively replaced by non-extractive approaches. For instance, species abundance indices can be calculated using data obtained from high-definition underwater cameras that enable to identify taxa at low taxonomical level. In biodiversity studies, environmental DNA (eDNA) has proven to be a useful tool for characterising fish species richness. However, several marine phyla remain poorly represented in reference gene databases or release limited amounts of DNA, restricting their detection. The absence of amplification of some invertebrate taxa might also reflect primer bias. We here explore and compare the performance of eDNA and image data in describing the marine communities of several sites in the Bay of Biscay. This was achieved by deploying a remotely operated vehicle to both record images and collect seawater samples. A total of 88 taxa were identified from the eDNA samples and 121 taxa from the images. For both methods, the best characterised phylum was Chordata, with 29 and 27 Actinopterygii species detected using image versus eDNA, respectively. Neither Bryozoa nor Cnidaria was detected in the eDNA samples while the phyla were easily identifiable by imagery. Similarly, Asteroidea (Echinodermata) and Cephalopoda (Mollusca) were scarcely detected in the eDNA samples but present on the images, while Annelida were mostly identified by eDNA (18 taxa vs 7 taxa from imagery). The complementary community descriptions we highlight from these two methods therefore advocate for using both eDNA and imagery in tandem in order to capture the macroscopic biodiversity of bentho-demersal marine communities.

Sec61 channel subunit Sbh1/Sec61ß promotes ER translocation of proteins with suboptimal targeting sequences and is fine-tuned by phosphorylation.

The highly conserved endoplasmic reticulum (ER) protein translocation channel contains one nonessential subunit, Sec61ß/Sbh1, whose function is poorly understood so far. Its intrinsically unstructured cytosolic domain makes transient contact with ER-targeting sequences in the cytosolic channel vestibule and contains multiple phosphorylation sites suggesting a potential for regulating ER protein import. In a microscopic screen, we show that 12% of a GFP-tagged secretory protein library depends on Sbh1 for translocation into the ER. Sbh1-dependent proteins had targeting sequences with less pronounced hydrophobicity and often no charge bias or an inverse charge bias which reduces their insertion efficiency into the Sec61 channel. We determined that mutating two N-terminal, proline-flanked phosphorylation sites in the Sbh1 cytosolic domain to alanine phenocopied the temperature-sensitivity of a yeast strain lacking SBH1 and its ortholog SBH2. The phosphorylation site mutations reduced translocation into the ER of a subset of Sbh1-dependent proteins, including enzymes whose concentration in the ER lumen is critical for ER proteostasis. In addition, we found that ER import of these proteins depended on the activity of the phospho-S/T-specific proline isomerase Ess1 (PIN1 in mammals). We conclude that Sbh1 promotes ER translocation of substrates with suboptimal targeting sequences and that its activity can be regulated by a conformational change induced by N-terminal phosphorylation.

Virtual Scoliosis Surgery Using a 3D-Printed Model Based on Biplanar Radiographs.

The aim of this paper is to describe a protocol that simulates the spinal surgery undergone by adolescents with idiopathic scoliosis (AIS) by using a 3D-printed spine model. Patients with AIS underwent pre- and postoperative bi-planar low-dose X-rays from which a numerical 3D model of their spine was generated. The preoperative numerical spine model was subsequently 3D printed to virtually reproduce the spine surgery. Special consideration was given to the printing materials for the 3D-printed elements in order to reflect the radiopaque and mechanical properties of typical bones most accurately. Two patients with AIS were recruited and operated. During the virtual surgery, both pre- and postoperative images of the 3D-printed spine model were acquired. The proposed 3D-printing workflow used to create a realistic 3D-printed spine suitable for virtual surgery appears to be feasible and reliable. This method could be used for virtual-reality scoliosis surgery training incorporating 3D-printed models, and to test surgical instruments and implants.

Is Gestational Diabetes Mellitus a Risk Factor of Maternal Breast Cancer? A Systematic Review of the Literature.

The association between gestational diabetes mellitus (GDM) and breast cancer (BC) risk is complex. We aimed to examine this association in a systematic review of the literature. This review was done using the PubMed/Medline and Web of Science databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Newcastle-Ottawa Scale was used for the assessment of bias and quality of studies. Only English-language articles published before 1 June 2021, were included. Fourteen studies were included in this systematic review. Among them, eight did not find statistically significant results. Three studies showed a statistically significant increased risk of BC after GDM, and they explained this potential increased risk by hyperinsulinemia, hyperglycemia, and low-grade inflammation. However, three studies showed a statistically significant decreased risk of BC after GDM, suggesting a possible protective effect of hormonal changes induced by GDM during pregnancy. These controversial results should be interpreted with caution due to both quantitative and qualitative methodological shortcomings. Further investigations are thus needed in order to gain a better understanding of the associations between GDM and BC, and their underlying mechanisms.

High temperature corrosion memory in a waste fired boiler - Influence of sulfur.

The selection of fuel for a Combined Heat and Power (CHP) plant can vary over time. By choosing less expensive fuels, operation costs are reduced, however, cheaper fuels generally increase corrosion maintenance costs. The corrosiveness of different fuels has been studied extensively while how the current corrosion attack is influenced by corrosion history, i.e. previous deposit build-up and oxide scale formation, is less studied. This phenomenon may be referred to as a "corrosion memory" effect (Paz et al., 2017). The present work investigates the influence of addition of sulfur to the fuel on the corrosion memory through air-cooled probes in the Waste-to Energy lines at Måbjerg Energy Center (MEC) in Denmark. The results show a corrosion memory effect, i.e. as initially corrosive environment may increase the subsequent corrosion rate and vice versa.

Increased Risk of Hospitalization for Pancreatic Cancer in the First 8 Years after a Gestational Diabetes Mellitus regardless of Subsequent Type 2 Diabetes: A Nationwide Population-Based Study.

The aim of this large retrospective cohort study was to use a quasi-exhaustive national medico-administrative database of deliveries in France to determine the risk of developing pancreatic cancer (PC) in women with a history of gestational diabetes mellitus (GDM). This nationwide population-based study included women aged 14-55 who gave birth between 1st January 2008 and 31 December 2009. The women were followed-up epidemiologically for eight years. Survival analyses using Cox regression models, adjusted for age, subsequent type 2 diabetes, and tobacco consumption, were performed on the time to occurrence of hospitalization for PC. The onset of GDM, tobacco consumption and subsequent type 2 diabetes were considered as time-dependent variables. Among 1,352,560 women included, 95,314 had a history of GDM (7.05%) and 126 women were hospitalized for PC (0.01%). Over the eight years of follow-up, GDM was significantly associated with a higher risk of hospitalization with PC in the first Cox regression model adjusted for age and subsequent type 2 diabetes (HR = 1.81 95% CI [1.06-3.10]). The second Cox regression model adjusted for the same covariates, plus tobacco consumption, showed that GDM was still significantly associated with a higher risk of hospitalization for PC with nearly the same estimated risk (HR = 1.77 95% CI [1.03-3.03]). Gestational diabetes was significantly associated with a greater risk of hospital admission for pancreatic cancer within eight years, regardless of subsequent type 2 diabetes.

A methodological framework for characterizing fish swimming and escapement behaviors in trawls.

Knowledge about fish behavior is crucial to be able to influence the capture process and catch species composition. The rapid expansion of the use of underwater cameras has facilitated unprecedented opportunities for studying the behavior of species interacting with fishing gears in their natural environment. This technological advance would greatly benefit from the parallel development of dedicated methodologies accounting for right-censored observations and variable observation periods between individuals related to instrumental, environmental and behavioral events. In this paper we proposed a methodological framework, based on a parametric Weibull mixture model, to describe the process of escapement attempts through time, test effects of covariates and estimate the probability that a fish will attempt to escape. We additionally proposed to better examine the escapement process at the individual level with regard to the temporal dynamics of escapement over time. Our approach was used to analyze gadoids swimming and escapement behaviors collected using a video set up in front of a selective device known to improve selectivity on gadoids in the extension of a bottom trawl. Comparison of the fit of models indicates that i) the instantaneous rate of escape attempts is constant over time and that the escapement process can be modelled using an exponential law; ii) the mean time before attempting to escape increases with the increasing number of attempts; iii) more than 80% of the gadoids attempted to escape through the selective device; and iv) the estimated probability of success was around 15%. Effects of covariates on the probability of success were investigated using binomial regression but none of them were significant. The data set collected is insufficient to make general statements, and further observations are required to properly investigate the effect of intrinsic and extrinsic factors governing gadoids behavior in trawls. This methodology could be used to better characterize the underlying behavioral process of fish in other parts of a bottom trawl or in relation to other fishing gears.

The low impact of fish traps on the seabed makes it an eco-friendly fishing technique.

Besides understanding the effects of fishing on harvested fish stocks, effects on non-target species, habitats and seafloor integrity also need to be considered. Static fishing gears have often been mentioned as a lower impact fishing alternative to towed gears, although studies examining their actual impact on the seafloor are scarce. In this study, we aimed to describe fish trap movements on the seafloor related to soaking time and trap retrieval. Impacts on the seafloor of lightweight rectangular traps and heavier circular traps were compared. We used 3D video cameras to estimate sweeping motion on the seabed and penetration into the sediment during soaking time. The area and distance swept by each type of trap during retrieval was determined by a camera set up facing the sea bottom. The potential rotation of the traps around the mainline was assessed using an Acoustic Doppler Current Profiler. Results showed that no penetration and almost no movements could be detected during soaking time for either lightweight or heavy commercial traps, even for high tidal coefficient (maximum 6 cm). No rotation could be observed when the tide turned. The swept area covered by a trap during retrieval was low (maximum 2.04 m2) compared to towed fishing gear and other static gear.

Survival in patients with HR+/HER2- metastatic breast cancer treated with initial endocrine therapy versus initial chemotherapy. A French population-based study.

BACKGROUND: According to international guidelines, endocrine therapy (ET) is the preferred option for hormone receptor-positive (HR+) HER2-negative (HER2-) metastatic breast cancer. In spite of clear recommendations, these are not strictly followed in daily practice. The objectives of this study were to investigate the effect of the first anti-metastatic treatment therapy choice on progression-free survival (PFS) and overall survival (OS). METHODS: In this population-based study, we included patients with HR+/HER2- metastatic breast cancer recorded in the Côte d'Or Breast Cancer Registry. Differences in PFS and OS between patients initially treated with chemotherapy (CT) or ET were analysed in Cox proportional hazards models. In a sensitivity analysis, we used a propensity score (PS) to limit the indication bias. RESULTS: Altogether, 557 cases were included, 280 received initial ET and 277 received initial CT. PFS and OS in patients initially treated with ET was improved significantly when compared to patients with initial CT (respectively, HR = 0.83 (95% CI 0.69-0.99) and HR = 0.71 (95% CI 0.58-0.86)). The results of the sensitivity analysis supported these findings. CONCLUSION: This study shows that treating patients with HR+/HER2- metastatic breast cancer with initial ET could provide a survival advantage in comparison with initial CT.

Socio-economic and occupational outcomes of long-term survivors of gynaecological cancer: A French population-based study.

OBJECTIVE: To describe socio-economic and professional outcomes in long-term survivors of cervical, endometrial or ovarian cancer, including return to work and problems related to obtaining loans and insurance. METHODS: Women with cervical, endometrial or ovarian cancers diagnosed from 2006 to 2013 were selected through the French gynaecological cancer registry of Côte d'Or, in a cross-sectional survey. Using a questionnaire established with the help of sociologists and psychologists, social and cancer-related work issues were collected among women aged less than 60 years at the time of cancer diagnosis. The socio-economic status was also assessed, at the time of the survey using the EPICES questionnaire. RESULTS: A total of 92 gynaecological cancer survivors (CS) participated in this survey. Gynaecological CS reported a decrease in income since cancer diagnosis, difficulties obtaining loans, and a decrease in ability to work, both in the short term after treatment and at the time of survey, on average 6 years after diagnosis. Fatigue, emotional and cognitive difficulties were the reasons cited to explain the decreased ability to work, both immediately after treatment and in the long term. CONCLUSIONS: Gynaecological CS experienced many problems, such as decreased work capacity, decreased income and difficulty obtaining loans.

Enantiopure α-Trifluoromethylated Aziridine-2-carboxylic Acid (α-TfmAzy): Synthesis and Peptide Coupling.

A straightforward synthesis of enantiopure α-trifluoromethyl aziridine-2-carboxylic acid (α-TfmAzy) is reported from a trifluoropyruvate derived enantiopure oxazolidine. A key Strecker-type synthetic step and a late cyanide basic hydrolysis gave the target compounds in six steps and 41% yield. A final peptide coupling was performed to demonstrate the usefulness of this highly constrained fluorinated unnatural amino acid.

Long-Term Gynecological Cancer Survivors in Côte d'Or: Health-Related Quality of Life and Living Conditions.

BACKGROUND: The likelihood that health-related quality of life (HRQoL) could depend on factors other than clinical data increases with the duration of follow-up since diagnosis. The aim of this study was to identify determinants of long-term HRQoL in women with cervical, endometrial, and ovarian cancer. Secondary objectives were to describe their living conditions (sexual function, psychological distress, social and professional reinsertion). MATERIALS AND METHODS: In a cross-sectional survey, women diagnosed with cervical, endometrial, and ovarian cancers from 2006 to 2013 were selected through the French gynecological cancers registry of Côte d'Or. Validated questionnaires exploring HRQoL (short-form health survey; SF-12), anxiety and depression (Hospital Anxiety and Depression Scale), social support (Sarason's Social Support Questionnaire), sexual function (Female Sexual Function Index), and living conditions (EPICES questionnaire) were used to assess HRQoL and its determinants. Social and professional reinsertion were also investigated using study-specific questionnaires. Determinants of HRQoL were identified using a multivariable mixed-regression model for each composite score of the SF-12. RESULTS: In total, 195 gynecological cancer survivors participated in the survey. HRQoL was deteriorated for almost all the SF-12 dimensions. The main determinants of poor HRQoL were comorbidities, deprivation, lack of availability and satisfaction with social support, and psychological outcomes. Thirty-four percent of survivors of gynecological cancer reported a negative impact of cancer on their work, and 73% reported an impaired ability to work after treatment. CONCLUSIONS: Long-term HRQoL of survivors of gynecological cancer is not impacted by stage of disease. Specific interventions should focus on issues that promote social and professional reintegration and improve HRQoL. IMPLICATIONS FOR PRACTICE: This study shows that women with gynecological cancer have problems related to work and sexual dysfunction, even 5 years after diagnosis. The results of this study will help improve clinicians' awareness of the factors affecting the lives of gynecological cancer survivors, even long after diagnosis and treatment. They will also highlight for clinicians the areas that are of importance to gynecological cancer survivors, making it possible to guide management of these patients with a view to preventing deteriorated health-related quality of life after treatment. For the health authorities, the results of this study underline that more than 5 years after gynecological cancer, the initial stage of disease no longer affects quality of life, but there is a clear need for actions targeting socio-professional reintegration of survivors.

Homochiral versus Heterochiral Trifluoromethylated Pseudoproline Containing Dipeptides: A Powerful Tool to Switch the Prolyl-Amide Bond Conformation.

The design of constrained peptides is of prime importance in the development of bioactive compounds and for applications in supramolecular chemistry. Due to its nature, the peptide bond undergoes a spontaneous cis-trans isomerism, and the cis isomers are much more difficult to stabilize than the trans forms. By using oxazolidine-based pseudoprolines (ΨPro) substituted by a trifluoromethyl group, we show that the cis peptide bond can be readily switched from 0% to 100% in Xaa-ΨPro dipeptides. Our results prove that changing the configuration of the Cα in Xaa or in ΨPro is sufficient to invert the cis:trans populations while changing the nature of the Xaa side chain finely tuned the conformers ratio. Moreover, a strong correlation is found between the puckering of the oxazolidine ring and the peptide bond conformation. This finding highlights the role of the trifluoromethyl group in the stabilization of the peptide bond geometry. We anticipate that such templates will be very useful to constrain the backbone geometry of longer peptides.

Incorporation of Trifluoromethylated Proline and Surrogates into Peptides: Application to the Synthesis of Fluorinated Analogues of the Neuroprotective Glycine-Proline-Glutamate (GPE) Tripeptide.

The incorporation into a peptide chain of highly hindered and weakly nucleophilic trifluoromethylated prolines, pseudoprolines and oxazolidines has been achieved. As an application, the synthesis of a new class of fluorinated analogues of the neuroprotective tripeptide glycine-proline-glutamate (GPE) is reported. These analogues have been elaborated from a panel of five-membered ring trifluoromethylated amino acids (Tfm-AAs) through the coupling reaction with a glutamate residue at the C-terminus and a glycine at the N-terminus. Although the peptide coupling reaction at the C-terminal position of the fluorinated amino acid was conveniently performed under standard conditions, the very challenging coupling reaction at the highly deactivated N-terminal position proved to be much more problematic. A methodological study was needed to identify suitable reaction conditions for this difficult peptide coupling.

Incorporation of CF3-pseudoprolines into peptides: a methodological study.

The peptide coupling reactions allowing the incorporation of trifluoromethyl substituted oxazolidine-type pseudoprolines (CF3-ΨPro) into peptide chains have been studied. While standard protocols can be used for the peptide coupling reaction at the C-terminal position of the CF3-ΨPro, acid chloride activation has to be used for the peptide coupling reaction at the N-terminal position to overcome the decrease of nucleophilicity of the CF3-ΨPro. We demonstrate that the N-amidification of a diastereomeric mixture of CF3-ΨPro using Fmoc-protected amino acid chloride without base gave the corresponding dipeptides as a single diastereomer (6 examples). The ratio of the cis and trans amide bond conformers was determined by NMR study, highlighting the role of the Xaa side chains in the control of the peptide backbone conformation. Finally a tripeptide bearing a central CF3-ΨPro has been successfully synthesized.

Highly diastereoselective synthesis of enantiopure ß-trifluoromethyl ß-amino alcohols from chiral trifluoromethyl oxazolidines (Fox).

The organolithium species addition to 2-hydroxymethyl fluorinated oxazolidines (Fox) provides a highly diastereoselective and straightforward route for the synthesis of enantiopure trifluoromethyl ß-amino alcohols quaternarized at the ß-position.