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Abstract Background In this study, we investigated whether the association of curcumin and docetaxel among advanced and metastatic breast cancer patients in first or second‐line treatment potentiated the objective response rate. Patients/Methods A multicentre, randomized, open label, phase‐II study was conducted and included 42 patients from July 2009 to January 2017. The primary endpoint was the objective response rate of the docetaxel‐curcumin combination in comparison with docetaxel alone. The secondary endpoints were the assessment of clinical benefit, overall survival, time‐to‐progression, progression‐free survival, compliance, and safety. An interim analysis was planned to evaluate safety and efficacy. Results In this interim analysis conducted on 37 patients (19 in the control group vs. 18 in the experimental group), no difference was observed for the objective response rate (p = 0.25, control 73.7% vs. experimental 55.6%). Concerning clinical benefit, overall survival and time‐to‐progression, we also failed to show any difference between the two arms. A slight tendency towards longer progression‐free survival at 12 months after randomization was observed in the curcumin group (65.5% vs. 41.4%) but this difference did not reach significance (p = 0.14). Conclusion In this study, we showed for the first time that adding oral curcumin for advanced and metastatic breast cancer patients treated with first or second‐line docetaxel was not efficacious, although safe. Consequently, this study was stopped for reasons of futility. Further studies with a larger number of patients, a different curcumin preparation, a longer treatment period and a pharmacokinetic evaluation of curcumin are needed to explore the real efficacy of this compound.

Background: Drug hypersensitivity reactions (DHRs) are becoming more common as a result of increasing prevalence and case complexity. Allergists and clinical immunologists worldwide are challenged daily to adequately diagnose and manage these reactions. Data in the literature regarding DHR outpatient consultations are scarce worldwide, limited in the Middle East, and currently unavailable in Lebanon. Objective: This retrospective study aimed to evaluate the characteristics of all reported DHRs over 10 years in a tertiary-care allergy clinic in Lebanon. Methods: We conducted a decade-long (2012-21) retrospective analysis of the archived medical records of patients with a history of DHRs. Demographics, clinical history, diagnostic tools, and characteristics of the DHRs were collected and analyzed. Results: A total of 758 patients experienced DHRs to therapeutic molecules provided for ambulatory care. Our results identified 72 medications. The most frequently implicated drug classes included β-lactam antibiotics (53.8%), followed closely by nonsteroidal anti-inflammatory drugs (48.9%). Of the 758 patients, 32.6% reported DHRs to multiple molecules, and 11.8% reported concomitant DHRs to 1 or several molecules provided in the perioperative setting. Of those, opioids and neuromuscular blocking agents were the 2 most common therapeutic classes. Furthermore, we evaluated the cross-reactivity between molecules of the same class. In neuromuscular blocking agents, rocuronium and cisatracurium were the most commonly cross-reactive, and for opioids, the most common association we recorded was with morphine and pethidine. Conclusion: Our findings constitute the first step toward a more comprehensive evaluation of the clinical characteristics of DHRs in Lebanon.

Abstract X-ray Absorption Spectroscopy (XAS) is a widely used X-ray diagnostic method for studying electronic and structural properties of matter. At first glance, the relatively narrow bandwidth and the highly fluctuating spectral structure of X-ray Free Electron Lasers (XFEL) sources seem to require accumulation over many shots to achieve high data quality. To date the best approach to implementing XAS at XFEL facilities has been using monochromators to scan the photon energy across the desired spectral range. While this is possible for easily reproducible samples such as liquids, it is incompatible with many important systems. Here, we demonstrate collection of single-shot XAS spectra over 10s of eV using an XFEL source, with error bars of only a few percent. We additionally show how to extend this technique over wider spectral ranges towards Extended X-ray Absorption Fine Structure measurements, by concatenating a few tens of single-shot measurements. Our results pave the way for future XAS studies at XFELs, in particular those in the femtosecond regime. This advance is envisioned to be especially important for many transient processes that can only be initiated at lower repetition rates, for difficult to reproduce excitation conditions, or for rare samples, such as those encountered in high-energy density physics.

Abstract The structures, strain fields, and defect distributions in solid materials underlie the mechanical and physical properties across numerous applications. Many modern microstructural microscopy tools characterize crystal grains, domains and defects required to map lattice distortions or deformation, but are limited to studies of the (near) surface. Generally speaking, such tools cannot probe the structural dynamics in a way that is representative of bulk behavior. Synchrotron X-ray diffraction based imaging has long mapped the deeply embedded structural elements, and with enhanced resolution, dark field X-ray microscopy (DFXM) can now map those features with the requisite nm-resolution. However, these techniques still suffer from the required integration times due to limitations from the source and optics. This work extends DFXM to X-ray free electron lasers, showing how the $$10^{12}$$ 10 12 photons per pulse available at these sources offer structural characterization down to 100 fs resolution (orders of magnitude faster than current synchrotron images). We introduce the XFEL DFXM setup with simultaneous bright field microscopy to probe density changes within the same volume. This work presents a comprehensive guide to the multi-modal ultrafast high-resolution X-ray microscope that we constructed and tested at two XFELs, and shows initial data demonstrating two timing strategies to study associated reversible or irreversible lattice dynamics.

Abstract The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.

Abstract Background Weight change during chemotherapy is reported to be associated with a worse prognosis in breast cancer patients, both with weight gain and weight loss. However, most studies were conducted prior to the common use of anthracycline-base chemotherapy and on North American populations with a mean BMI classified as overweight. Our study was aimed to evaluate the prognostic value of weight change during anthracycline-based chemotherapy on non metastatic breast cancer (European population) with a long term follow-up. Methods Patients included 111 women diagnosed with early stage breast cancer and locally advanced breast cancer who have been treated by anthracycline-based chemotherapy regimen between 1976 and 1989. The relative percent weight variation (WV) between baseline and postchemotherapy treatment was calculated and categorized into either weight change (WV > 5%) or stable (WV < 5%). The median follow-up was 20.4 years [19.4 - 27.6]. Cox proportional hazard models were used to evaluate any potential association of weight change and known prognostic factors with the time to recurrence and overall survival. Results Baseline BMI was 24.4 kg/m2 [17.1 - 40.5]. During chemotherapy treatment, 31% of patients presented a notable weight variation which was greater than 5% of their initial weight. In multivariate analyses, weight change (> 5%) was positively associated with an increased risk of both recurrence (RR 2.28; 95% CI: 1.29-4.03) and death (RR 2.11; 95% CI: 1.21-3.66). Conclusions Our results suggest that weight change during breast-cancer chemotherapy treatment may be related to poorer prognosis with higher reccurence and higher mortality in comparison to women who maintained their weight.

Superconductivity in the cuprates is known to be intertwined with charge and spin density waves. Here, the authors study the prototypical cuprate La1.885Sr0.115CuO4 via x-ray scattering and discover a sudden increase in the charge-density-wave amplitude upon entering the superconducting-vortex-liquid state at high magnetic field.

Abstract Background Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m2). Case presentation We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. Conclusion Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency.

School-based interventions for the prevention of dating and relationship violence (DRV) and gender-based violence (GBV) take advantage of universal opportunities for intervention. Information on differential effectiveness of interventions is important to assess if they ameliorate or worsen social gradients in specific outcomes. This is especially important in DRV and GBV prevention given the gendered context of these behaviours and their common aetiologies in patriarchal gender norms, and social acceptance in school contexts of sexual harassment, such as catcalling or unwanted groping. We undertook a systematic review of moderation analyses in randomised trials of school-based interventions for DRV and GBV prevention. We searched 21 databases and used supplementary search methods without regard to publication type, language or year of publication, and synthesised moderation tests relating to equity-relevant characteristics (principally sex and prior history of the outcome) for DRV and GBV perpetration and victimisation. Across 23 included outcome evaluations, programme effects on DRV victimisation were not moderated by gender or prior experience of DRV victimisation, but DRV perpetration outcomes were greater for boys, particularly for emotional and physical DRV perpetration. Findings for GBV outcomes were counterintuitive. Our findings suggest that practitioners should carefully monitor local intervention effectiveness and equity to ensure that interventions are working as intended. However, one of the most surprising findings from our analysis—with clear relevance for uncertainties in practice—was that differential impacts by sexuality or sexual minority status were not frequently evaluated.

Abstract Objective: To quantify the change in availability of hyper-palatable foods (HPF) in the US foods system over 30 years (1988–2018). Design: Three datasets considered representative of the US food system were used in analyses to represent years 1988, 2001 and 2018. A standardised definition from Fazzino et al. (2019) that specifies combinations of nutrients was used to identify HPF. Setting: Analysis of food-item level data was conducted. Differences in the prevalence of HPF were characterised by Cochran’s Q and McNemar’s tests. Generalised linear mixed models with a fixed effect for time and random intercept for food item estimated change in the likelihood that a food was classified as hyper-palatable over time. Participants: No participant data were used. Results: The prevalence of HPF increased 20 % from 1988 to 2018 (from 49 % to 69 %; P < 0·0001). The most prominent difference was in the availability of HPF high in fat and Na, which evidenced a 17 % higher prevalence in 2018 compared with 1988 (P < 0·0001). Compared with 1988, the same food items were >2 times more likely to be hyper-palatable in 2001, and the same food items were >4 times more likely to be classified as hyper-palatable in 2018 compared with 1988 (P values < 0·0001). Conclusions: The availability of HPF in the US food system increased substantially over 30 years. Existing food products in the food system may have been reformulated over time to enhance their palatability.

Summary: Arterialized venous flaps (AVFs) are an innovative option in hand reconstruction. Their exact vascular physiology and survival mechanisms remain unclear. We report on two hand reconstruction cases with AVFs. Indocyanine green laser angiography was used to assess vascular perfusion of the flaps. A notable change in flap perfusion was seen by 48 h post-operatively with normalization of shunting and progression to a diffuse perfusion pattern resembling traditional flaps. Flap survival was attributed to reversed shunting at the microvascular level occurring within the first 48 h post-operatively.

Charge and spin density waves describe periodic distortions to the electronic structure of a given system and ultrafast laser techniques can provide unique mechanistic insight into their underling physics. Here, the authors use femtosecond laser pulses to understand the role phonon dynamics play in the formation of a spin density wave in Cr thin films.

Acute myeloid leukemia (AML) with BCR::ABL1 has recently been recognized as a distinct subtype in international classifications. Distinguishing it from myeloid blast crisis chronic myeloid leukemia (BC-CML) without evidence of a chronic phase (CP), remains challenging. We aimed to better characterize this entity by integrating clonal architecture analysis, mutational landscape assessment, and gene expression profiling. We analyzed a large retrospective cohort study including CML and AML patients. Two AML patients harboring a BCR::ABL1 fusion were included in the study. We identified BCR::ABL1 fusion as a primary event in one patient and a secondary one in the other. AML-specific variants were identified in both. Real-time RT-PCR experiments demonstrated that CD25 mRNA is overexpressed in advanced-phase CML compared to AML. Unsupervised principal component analysis showed that AML harboring a BCR::ABL1 fusion was clustered within AML. An AML vs. myeloid BC-CML differential expression signature was highlighted, and while ID4 (inhibitor of DNA binding 4) mRNA appears undetectable in most myeloid BC-CML samples, low levels are detected in AML samples. Therefore, CD25 and ID4 mRNA expression might differentiate AML with BCR::ABL1 from BC-CML and assign it to the AML group. A method for identifying this new WHO entity is then proposed. Finally, the hypothesis of AML with BCR::ABL1 arising from driver mutations on a BCR::ABL1 background behaving as a clonal hematopoiesis mutation is discussed. Validation of our data in larger cohorts and basic research are needed to better understand the molecular and cellular aspects of AML with a BCR::ABL1 entity.

(1) Background: Since the emergence of SARS-CoV-2, responsible for the COVID-19 pandemic, efforts have been made to identify antiviral compounds against human coronaviruses. With the aim of increasing the diversity of molecule scaffolds, 42 natural compounds, of which 28 were isolated from lichens and 14 from their associated microorganisms (bacteria and fungi), were screened against human coronavirus HCoV-229E. (2) Methods: Antiviral assays were performed using HCoV-229E in Huh-7 and Huh-7/TMPRSS2 cells and SARS-CoV-2 in a Vero-81-derived clone with a GFP reporter probe. (3) Results: Four lichen compounds, including chloroatranol, emodin, perlatolic acid and vulpinic acid, displayed high activities against HCoV-229E (IC50 = 68.86, 59.25, 16.42 and 14.58 μM, respectively) and no toxicity at active concentrations. Kinetics studies were performed to determine their mode of action. The four compounds were active when added at the replication step. Due to their significant activity, they were further tested on SARS-CoV-2. Perlatolic acid was shown to be active against SARS-CoV-2. (4) Conclusions: Taken together, these results show that lichens are a source of interesting antiviral agents against human coronaviruses. Moreover, perlatolic acid might be further studied for its pan-coronavirus antiviral activity.

The immune system offers several mechanisms of response to harmful microbes that invade the human body. As a first line of defense, neutrophils can remove pathogens by phagocytosis, inactivate them by the release of reactive oxygen species (ROS) or immobilize them by neutrophil extracellular traps (NETs). Although recent studies have shown that bacteriophages (phages) make up a large portion of human microbiomes and are currently being explored as antibacterial therapeutics, neutrophilic responses to phages are still elusive. Here, we show that exposure of isolated human resting neutrophils to a high concentration of the Pseudomonas phage PAK_P1 led to a 2-fold increase in interleukin-8 (IL-8) secretion. Importantly, phage exposure did not induce neutrophil apoptosis or necrosis and did not further affect activation marker expression, oxidative burst, and NETs formation. Similarly, inflammatory stimuli-activated neutrophil effector responses were unaffected by phage exposure. Our work suggests that phages are unlikely to inadvertently cause excessive neutrophil responses that could damage tissues and worsen disease. Because IL-8 functions as a chemoattractant, directing immune cells to sites of infection and inflammation, phage-stimulated IL-8 production may modulate some host immune responses.

PurposeOut-of-hospital cardiac arrest (OHCA) has a poor prognosis, with an overall survival rate of about 5% at discharge. Shockable rhythm cardiac arrests (ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have a better prognosis. In case of shockable rhythm, treatment is based on defibrillation, and thereafter, in case of failure of 3 external electric shocks (EES), on direct intravenous administration of 300 mg amiodarone, or lidocaine when amiodarone is unavailable or inefficient. During surgical procedures under extracorporeal circulation, a high potassium cardioplegia solution is administered to interrupt cardiac activity and facilitate surgical procedure. By extension, direct intravenous administration of potassium chloride (KCl) has been shown to convert VF, resulting in return to a hemodynamically efficient organized heart rate within a few minutes. The aim of this study is to provide clinical evidence that direct intravenous injection of KCl, into a patient presenting with OHCA due to refractory VF although 3 EES, should interrupt this VF and then allow rapid restauration of an organized heart rhythm, and thus return of spontaneous circulation (ROSC).MethodsA multicenter, prospective, single group, phase 2 study will be conducted on 81 patients presenting with refractory VF. After failure of 3 EES, each patient will receive direct intravenous injection of 20 mmol KCl instead of amiodarone. The primary outcome will be survival rate at hospital admission. Major secondary outcomes will include ROSC and time to ROSC in the prehospital setting, number of VF recidivism after KCl injection, survival rate at hospital discharge with a good neurologic prognostic, and survival rate 3 months after hospital discharge with a good neurologic prognostic.ResultsNo patient is currently included in the study.DiscussionConventional guideline strategy based on antiarrhythmic drug administration, i.e. amiodarone or lidocaine, for OHCA due to shockable rhythm, has not yet demonstrated an increase in survival at hospital admission or at hospital discharge. This may be related to the major cardiodepressant effect of those drugs.Trial registrationClinicalTrials.gov Identifier: NCT04316611. Registered on March 2020. AP-HP180577 / N° EUDRACT: 2019-002544-24. Funded by the French Health Ministry. https://clinicaltrials.gov/ct2/show/NCT04316611.

Background School cafeterias are a major point of influence for child nutrition. United States federal legislation requires the presence of important nutrients in school meals. However, legislation overlooks the potential presence of hyper-palatable foods in school lunches, a hypothesized factor that may influence children’s eating behavior and obesity risk. The study sought to 1) quantify the prevalence of hyper-palatable foods (HPF) served in US elementary school lunches; and 2) determine whether food hyper-palatability varied based on school geographic region (East/Central/West), urbanicity (urban/micropolitan/rural), or meal item (entrée/side/fruit or vegetable). Methods Lunch menu data (N = 18 menus; N = 1160 total foods) were collected from a sample of six states that represented geographic regions of the United States (Eastern/Central/Western; Northern/Southern) and that had variability in urbanicity (urban, micropolitan, and rural) within each state. A standardized definition from Fazzino et al (2019) was used to identify HPF in lunch menus. Results HPF comprised almost half of foods in school lunches (M = 47%; SD = 5%). Compared to fruit/vegetable items, entrées were >23 times more likely to be hyper-palatable and side dishes were >13 times more likely to be hyper-palatable (p values < .001). Geographic region and urbanicity were not significantly associated with food item hyper-palatability (p values >.05). The majority of entrée and side items contained meat/meat alternatives and/or grains and likely aligned with the US federal reimbursable meal components of meat/meat alternatives and/or grains. Conclusions and implications HPF comprised almost half of foods offered in elementary school lunches. Entrées and side items were most likely to be hyper-palatable. US school lunches may be a key point of regular exposure to HPF among young children, a risk factor that may elevate child obesity risk. Public policy regulating HPF in school meals may be needed to protect children’s health.

BackgroundSchool cafeterias are a major point of influence for child nutrition. United States federal legislation requires the presence of important nutrients in school meals. However, legislation overlooks the potential presence of hyper-palatable foods in school lunches, a hypothesized factor that may influence children's eating behavior and obesity risk. The study sought to 1) quantify the prevalence of hyper-palatable foods (HPF) served in US elementary school lunches; and 2) determine whether food hyper-palatability varied based on school geographic region (East/Central/West), urbanicity (urban/micropolitan/rural), or meal item (entrée/side/fruit or vegetable).MethodsLunch menu data (N = 18 menus; N = 1160 total foods) were collected from a sample of six states that represented geographic regions of the United States (Eastern/Central/Western; Northern/Southern) and that had variability in urbanicity (urban, micropolitan, and rural) within each state. A standardized definition from Fazzino et al (2019) was used to identify HPF in lunch menus.ResultsHPF comprised almost half of foods in school lunches (M = 47%; SD = 5%). Compared to fruit/vegetable items, entrées were >23 times more likely to be hyper-palatable and side dishes were >13 times more likely to be hyper-palatable (p values < .001). Geographic region and urbanicity were not significantly associated with food item hyper-palatability (p values >.05). The majority of entrée and side items contained meat/meat alternatives and/or grains and likely aligned with the US federal reimbursable meal components of meat/meat alternatives and/or grains.Conclusions and implicationsHPF comprised almost half of foods offered in elementary school lunches. Entrées and side items were most likely to be hyper-palatable. US school lunches may be a key point of regular exposure to HPF among young children, a risk factor that may elevate child obesity risk. Public policy regulating HPF in school meals may be needed to protect children's health.

The bleeding phenotype of hereditary coagulation disorders is caused by the low or undetectable activity of the proteins involved in hemostasis, due to a broad spectrum of genetic alterations. Most of the affected coagulation factors are produced in the liver. Therefore, two-dimensional (2D) cultures of primary human hepatocytes and recombinant overexpression of the factors in non-human cell lines have been primarily used to mimic disease pathogenesis and as a model for innovative therapeutic strategies. However, neither human nor animal cells fully represent the hepatocellular biology and do not harbor the exact genetic background of the patient. As a result, the inability of the current in vitro models in recapitulating the in vivo situation has limited the studies of these inherited coagulation disorders. Induced Pluripotent Stem Cell (iPSC) technology offers a possible solution to overcome these limitations by reprogramming patient somatic cells into an embryonic-like pluripotent state, thus giving the possibility of generating an unlimited number of liver cells needed for modeling or therapeutic purposes. By combining this potential and the recent advances in the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, it allows for the generation of autologous and gene corrected liver cells in the form of three-dimensional (3D) liver organoids. The organoids recapitulate cellular composition and organization of the liver, providing a more physiological model to study the biology of coagulation proteins and modeling hereditary coagulation disorders. This advanced methodology can pave the way for the development of cell-based therapeutic approaches to treat inherited coagulation disorders. In this review we will explore the use of liver organoids as a state-of-the-art methodology for modeling coagulation factors disorders and the possibilities of using organoid technology to treat the disease.

IntroductionThe impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).MethodsTo determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.ResultsNo global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.DiscussionThese results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.

The emerging SARS-CoV-2 virus has affected the entire world with over 600 million confirmed cases and 6.5 million deaths as of September 2022. Since the beginning of the pandemic, several variants of SARS-CoV-2 have emerged, with different infectivity and virulence. Several studies suggest an important role of neutrophils in SARS-Cov-2 infection severity, but data about direct activation of neutrophils by the virus is scarce. Here, we studied the in vitro activation of human neutrophils by SARS-CoV-2 variants of concern (VOCs). In our work, we show that upon stimulation with SARS-Cov-2 infectious particles, human healthy resting neutrophils upregulate activation markers, degranulate IL-8, produce Reactive Oxygen Species and release Neutrophil Extracellular Traps. Neutrophil activation was dependent on TLR7/8 and IRF3/STING. We then compared the activation potential of neutrophils by SARS-CoV-2 variants and showed a significantly increased activation by the Delta variant and a decreased activation by the Omicron variant as compared to the initial strain. In this study, we demonstrate that the SARS-Cov-2 virus can directly activate neutrophils in COVID-19 and that the different VOCs had differences in neutrophil activation intensity that mirror the differences of clinical severity. These data highlight the need to address neutrophil-virus interactions as a potential target for therapeutic intervention in SARS-CoV-2 infection.

AimWe aimed to describe the characteristics of individuals infected by BA.4 or BA.5 in France in comparison to BA.1, and analyze the factors associated with hospitalization among BA.4 and BA.5 cases.MethodsA standardized questionnaire was used to collect information on confirmed and probable Omicron cases. Hospitalization risk factors among BA.4/BA.5 cases were analyzed using Poisson regression. Variables with a p-value below 0.2 in the univariate analysis and a priori confounders were included in the multivariable regression model.ResultsThe median age of the 301 cases investigated was 47 years and 97% of cases were symptomatic. The most common clinical signs were asthenia/fatigue (75.7%), cough (58.3%), fever (58.3%), headache (52.1%) and rhinorrhea (50.7%). Twelve cases were hospitalized, and 27.1% reported risk factors. No admissions to intensive care and no deaths were reported. Vaccination status was available for 292 cases, 20.9% were unvaccinated, 1.4% had received one dose, 38.3% two doses and 39.4% three doses. Cases presenting at least one risk factor were almost seventeen times more likely to be hospitalized than those with no risk factors (aRR = 16.72 [95% CI2.59–326.86]).ConclusionDespite the longer duration of and the differences in symptoms and their possible immune escape, BA.4/BA.5 Omicron sub-lineages globally showed no severe clinical presentation. The presence of at least one risk factor for severe disease significantly increased the risk of hospitalization for those infected with BA.4 or BA.5.

Quaternary ammonium compounds (QAC) are commonly used disinfectants, antiseptics, preservatives, and detergents due to their antibacterial property and represent the first used biocides before phenolic or nitrogen products. Their common structure consists of one or more quaternary ammonium bound with four lateral substituents. Their amphiphilic structure allows them to intercalate into microorganism surfaces which induces an unstable and porous membrane that explains their antimicrobial activity towards bacteria, fungi, and viruses. QAC are thus found in many areas, such as household products, medicines, hygiene products, cosmetics, agriculture, or industrial products but are also used in medical practice as disinfectants and antiseptics and in health care facilities where they are used for cleaning floors and walls. QAC exposure has already been involved in occupational asthma in healthcare workers or professional cleaners by many authors. They also have been suggested to play a role in contact dermatitis (CD) and urticaria in workers using cosmetics such as hairdressers or healthcare workers, inciting reglementary agencies to make recommendations regarding those products. However, distinguishing the irritant or sensitizing properties of chemicals is complex and as a result, the sensitizing property of QAC is still controverted. Moreover, the precise mechanisms underlying the possible sensitization effect are still under investigation, and to date, only a few studies have documented an immunological mechanism. Besides, QAC have been suggested to be responsible for neuromuscular blocking agents (NMBA) sensitization by cross-reactivity. This hypothesis is supported by a higher prevalence of quaternary ammonium (QA)-specific IgE in the professionally exposed populations, such as hairdressers, cleaners, or healthcare workers, suggesting that the sensitization happens with structurally similar compounds present in the environment. This review summarizes the newest knowledge about QAC and their role in hypersensitivities. After describing the different QAC, their structure and use, the most relevant studies about the effects of QAC on the immune system will be reviewed and discussed.

Soon after the release of the new anti-COVID mRNA vaccines, reports came in from the US and the UK of anaphylactic reactions. Fueled by the necessary caution toward these new vaccine platforms, these reports had a great impact and were largely commented upon in the scientific literature and global media. The current estimated frequency is of 5 cases per million doses. Very little biological data are presented in the literature to support the anaphylaxis diagnosis in these patients in addition to skin tests. Allergic reactions to vaccines are rare and mostly due to vaccine excipient. Therefore, the poly-ethylene-glycol (PEG) present in both mRNA formulation, and already known to be immunogenic, was soon suspected to be the potential culprit. Several hypersensitivity mechanisms to PEG or to other vaccine components can be suspected, even if the classical IgE-dependent anaphylaxis seems to be one of the most plausible candidates. In the early 2022, the international guidelines recommended to perform skin prick tests and basophil activation tests (BAT) in people experiencing allergic reaction to the first dose of COVID-19 vaccine or with a history of PEG allergy. The aim of this review is to discuss the main potential mechanisms of immediate allergy to COVID19 vaccines based on published data, together with the various techniques used to confirm or not sensitization to one component.

Abstract Background Malignant pleural mesothelioma (MPM) is a rare, highly aggressive and deadly disease with a poor patient life expectancy. A few years ago, the main challenge was the histological diagnosis of this disease; at present, the search for the best therapeutic strategy is now a priority. However, an optimal therapeutic strategy is not yet clear, despite growing efforts in the treatment armamentarium and research, and at the era of tailored and individualized treatment, tools to predict patient survival are needed for therapeutic decision‐making. Among them, the LENT scoring system was developed to predict prognosis in patients with malignant pleural effusion. The aim of this study was to assess the performance of the LENT score in predicting prognosis in patients with MPM. Methods A retrospective observational study was conducted by analyzing the prospective collected databases of patients undergoing medical thoracoscopy in a single center with a final diagnosis of MPM confirmed by the MESOPATH National Reference Center. Results A total of 41 patients with MPM were studied. All patients underwent platinum‐based chemotherapy combined with pemetrexed ± bevacizumab. No high‐risk category patients were found using the LENT scoring system in this cohort. The median (range) LENT score at the time of medical thoracoscopy was 0 (0–3) and the median survival was 15.5 (2–54) months for the entire cohort. The median survival of low‐risk and moderate‐risk category patients was 21.4 months (2–54, 32 patients) and 6.7 months (2–19, nine patients), respectively. A total of 27 patients with MPM of epithelial subgroup had a median LENT score of 1 (0–2) with a 26 (2–54) months median survival. The median LENT score and median survival of nonepithelial mesothelioma patients (biphasic MPM subgroup, eight patients; sarcomatoid MPM subgroup, six patients) were 0 (0–3) and 11 (2–52) months, respectively. Conclusions Applied to a homogenous cohort of MPM patients, the LENT score underestimated prognosis and was not useful per se for the management of this disease, as evidenced in the epithelial mesothelioma subgroup of patients in our study.

The flat oyster Ostrea edulis is an oyster species native to Europe. It has declined to functional extinction in many areas of the NE Atlantic for several decades. Factors explaining this decline include over-exploitation of natural populations and diseases like bonamiosis, regulated across both the EU and the wider world and caused by the intracellular protozoan parasite Bonamia ostreae. To date, very limited sequence data are available for this Haplosporidian species. We present here the first transcriptome of B. ostreae. As this protozoan is not yet culturable, it remains extremely challenging to obtain high-quality -omic data. Thanks to a specific parasite isolation protocol and a dedicated bioinformatic pipeline, we were able to obtain a high-quality transcriptome for an intracellular marine micro-eukaryote, which will be very helpful to better understand its biology and to consider the development of new relevant diagnostic tools.

Abstract Background Metastatic castration‐resistant prostate cancer (mCRPC) patients have a poor prognosis, and curcumin is known to have antineoplastic properties. On the basis of previous phase I and phase II studies, we investigated whether the association of curcumin with docetaxel could improve prognosis among mCRPC patients. Methods A total of 50 mCRPC patients (included from June 2014 to July 2016) treated with docetaxel in association with oral curcumin (6 g/d for 7 days every 3 weeks) versus placebo were included in this double‐blind, randomized, phase II study. The primary endpoint was to evaluate the time to progression. Among the secondary endpoints, compliance, overall survival, prostate‐specific antigen (PSA) response, safety, curcumin absorption, and quality of life were investigated. An interim analysis was planned in the modified intention‐to‐treat population with data at 6 months (22 patients per arm). Results Despite good compliance and a verified absorption of curcumin, no difference was shown for our primary endpoint: progression‐free survival (PFS) between the placebo and curcumin groups was, respectively, 5.3 months versus 3.7 months, p = 0.75. Similarly, no difference was observed for the secondary objectives: PSA response rate (p = 0.88), overall survival (p = 0.50), and quality of life (p = 0.49 and p = 0.47). Conclusion Even though our previous studies and data in the literature seemed to support an association between curcumin and cancer therapies in order to improve patient outcome and prognosis, the results from this interim analysis clearly showed that adding curcumin to mCRPC patients’ treatment strategies was not efficacious. The study was discontinued on the grounds of futility.

Initial staging of patients diagnosed with multiple myeloma (MM) can lead to negative results using conventional diagnostic imaging workup, including [18F]Fluorodesoxiglucose ([18F]FDG) PET/CT. The aim of this prospective pilot study was to evaluate the diagnostic efficacy of [18F]Fluorocholine ([18F]FCH) PET/CT in the initial staging of MM patients who were candidates for autologous bone marrow transplant. Materials and Methods: The inclusion criteria of our study were: (a) patients diagnosed with MM; (b) candidates for autologous bone marrow transplant (AT); and (c) studied with [18F]FCH PET/CT and [18F]FDG PET/CT for initial staging less than 4 weeks apart. Imaging analysis included the presence of: bone marrow infiltration, focal bone lesions, and para-medullary or extra-medullary disease, according to the proposed IMPeTus criteria. The analysis was performed per lesion, per patient, and per location. Results: The study population included ten patients. Globally, [18F]FCH PET/CT showed bone marrow uptake in all the patients and visualised 16 more focal lesions than [18F]FDG PET/CT. One patient presented a plasmacytoma, detected by both tracers. Extra-medullary and para-medullary disease was identified with different degrees of uptake by both tracers. In summary, [18F]FCH PET seemed to be superior to [18F]FDG PET/CT in detecting focal bone lesions. SUVmax values were slightly higher in [18F]FCH PET/CT than in [18F]FDG PET/CT. Conclusions: Taking into account the small study population, according to our results, [18F]FCH PET/CT could be a useful tool for staging MM patients.

The production of parts by additive manufacturing is an important issue for the reduction in manufacturing costs and the creation of complex geometries. Optical inspection is often implemented in the machines during the manufacturing process in order to monitor the possible generated defects. However, it is also crucial to test the quality of the manufactured parts after their fabrication and monitor their health throughout their industrial lifetime. Therefore structural health monitoring (SHM) methods need to be studied or designed. In this paper, the eddy current method is used to control fabricated parts, as this technique is adapted to detect surface and shallow defects in conductive materials. Using simulations with the CIVA non-destructive testing software package, several sensors and their parameters were tested in order to determine the most optimal ones: a separate transmitter/receiver sensor and an isotropic sensor were finally designed. The comparison of these sensors’ efficiency was made on the detection of notches and engraved letters based on simulation and experimental tests on parts fabricated by laser powder bed fusion (L-PBF) in order to determine the optimal sensor. The various tests showed that the isotropic sensor is the optimal one for the detection and characterization of defects.

Immunotherapy is based on manipulation of the immune system in order to act against tumour cells, with growing evidence especially in melanoma patients. The challenges faced by this new therapeutic tool are (i) finding valid evaluation criteria for response assessment; (ii) knowing and distinguishing between “atypical” response patterns; (iii) using PET biomarkers as predictive and response evaluation parameters and (iv) diagnosis and management of immunorelated adverse effects. This review is focused on melanoma patients analysing (a) the role of [18F]FDG PET/CT in the mentioned challenges; (b) the evidence of its efficacy. For this purpose, we performed a review of the literature, including original and review articles. In summary, although there are no clearly established or globally accepted criteria, modified response criteria are potentially appropriate for evaluation of immunotherapy benefit. In this context, [18F]FDG PET/CT biomarkers appear to be promising parameters in prediction and assessment of response to immunotherapy. Moreover, immunorelated adverse effects are recognized as predictors of early response to immunotherapy and may be associated with better prognosis and clinical benefit.

Since life expectancy has increased significantly over the past century, society is being forced to discover innovative ways to support active aging and elderly care. The e-VITA project, which receives funding from both the European Union and Japan, is built on a cutting edge method of virtual coaching that focuses on the key areas of active and healthy aging. The requirements for the virtual coach were ascertained through a process of participatory design in workshops, focus groups, and living laboratories in Germany, France, Italy, and Japan. Several use cases were then chosen for development utilising the open-source Rasa framework. The system uses common representations such as Knowledge Bases and Knowledge Graphs to enable the integration of context, subject expertise, and multimodal data, and is available in English, German, French, Italian, and Japanese.

Mortality outbreaks of young Pacific oysters, Crassostrea gigas, have seriously affected the oyster-farming economy in several countries around the world. Although the causes of these mortality outbreaks appear complex, a viral agent has been identified as the main factor: a herpesvirus called ostreid herpesvirus 1 (OsHV-1). Autophagy is an important degradation pathway involved in the response to several pathologies including viral diseases. In C. gigas, recent studies indicate that this pathway is conserved and functional in at least haemocytes and the mantle. Furthermore, an experimental infection in combination with compounds known to inhibit or induce autophagy in mammals revealed that autophagy is involved in the response to OsHV-1 infection. In light of these results, the aim of this study was to determine the role of autophagy in the response of the Pacific oyster to infection by virus OsHV-1. For this purpose, an experimental infection in combination with a modulator of autophagy was performed on Pacific oysters known to have intermediate susceptibility to OsHV-1 infection. In haemolymph and the mantle, the autophagy response was monitored by flow cytometry, western blotting, and real-time PCR. At the same time, viral infection was evaluated by quantifying viral DNA and RNA amounts by real-time PCR. Although the results showed activation of autophagy in haemolymph and the mantle 14 hours post infection (after viral replication was initiated), they were also indicative of different regulatory mechanisms of autophagy in the two tissues, thus supporting an important function of autophagy in the response to virus OsHV-1.

Biodiversité et naturalité peuvent être considérées comme deux composantes distinctes et complémentaires des écosystèmes forestiers. Nous partons ici du constat que les relations entre ces deux composantes font encore souvent l’objet de débats, notamment lorsque les solutions basées sur la nature telles que la libre évolution sont proposées comme stratégies de conservation : biodiversité et naturalité n’évoluent pas invariablement dans le même sens et les écosystèmes avec la plus forte naturalité ne sont pas nécessairement les plus riches en biodiversité, ce qui peut conduire à la définition d’enjeux a priori contradictoire. Sur la base d’une revue de la littérature scientifique, nous proposons ici une analyse des réponses de la biodiversité aux quatre principaux gradients définissant la naturalité, à savoir les continuités spatiales et temporelles et la spontanéité dont nous distinguons deux formes, celle de fonctionnement et celle d’assemblage (ou d’origine). Ce travail bibliographique s’appuyant sur une définition pluridimensionnelle de la naturalité nous semble faciliter à la fois la synthèse des connaissances et l’identification des champs de recherches à investir dans le futur pour améliorer notre compréhension des enjeux de conservation des forêts.

We report the observation of photo-induced plasmon–phonon coupled modes in the group IV–VI semiconductor PbTe using ultrafast x-ray diffuse scattering at the Linac Coherent Light Source. We measure the near-zone-center excited-state dispersion of the heavily screened longitudinal optical (LO) phonon branch as extracted from differential changes in x-ray diffuse scattering intensity following above bandgap photoexcitation. We suggest that upon photoexcitation, the LO phonon-plasmon coupled (LOPC) modes themselves become coupled to longitudinal acoustic modes that drive electron band shifts via acoustic deformation potentials and possibly to low-energy single-particle excitations within the plasma and that these couplings give rise to displacement-correlations that oscillate in time with a period given effectively by the heavily screened LOPC frequency.

In this paper, we describe an interface reconstruction method in two dimension. This method is an extension of DPIR [1], which reconstructs continuous interfaces and preserves partial volumes using dynamic programming. First we extend the method to curved interfaces. Then, we present tools to improve its robustness in order to apply it to unstructured grid. Finally, we describe an extension to three materials.

BackgroundThe purpose of this study was to develop a swine model of surgically induced blood loss to evaluate the performances of a new autotransfusion system allowing red blood cells and platelets preservation while collecting, washing and concentrating hemorrhagic blood intraoperatively.MethodsTwo types of surgically induced blood loss were used in 12 minipigs to assess system performance and potential animal complications following autotransfusion: a cardiac model (cardiopulmonary bypass) and a visceral model (induced splenic bleeding). Animal clinical and hematological parameters were evaluated at different time-points from before bleeding to the end of a 72-hour post-transfusion period and followed by a post-mortem examination. System performances were evaluated by qualitative and quantitative parameters.ResultsAll animals that received the autotransfusion survived. Minimal variations were seen on the red blood cell count, hemoglobin, hematocrit at the different sampling times. Coagulation tests failed to show any hypo or hypercoagulable state. Gross and histologic examination didn't reveal any thrombotic lesions. Performance parameters exceeded set objectives in both models: heparin clearance (≥ 90%), final heparin concentration (≤ 0.5 IU/mL), free hemoglobin washout (≥ 90%) and hematocrit (between 45% and 65%). The device treatment rate of diluted blood was over 80 mL/min.ConclusionsIn the present study, both animal models succeeded in reproducing clinical conditions of perioperative cardiac and non-cardiac blood loss. Sufficient blood was collected to allow evaluation of autotransfusion effects on animals and to demonstrate the system performance by evaluating its capacity to collect, wash and concentrate red blood cells and platelets. Reinfusion of the treated blood, containing not only concentrated red blood cells but also platelets, did not lead to any postoperative adverse nor thrombogenic events. Clinical and comparative studies need to be conducted to confirm the clinical benefit of platelet reinfusion.

Breast cancer screening guidelines serve as crucial evidence-based recommendations in deciding when to begin regular screenings. However, due to developments in breast cancer research and differences in research interpretation, screening guidelines can vary between organizations and within organizations over time. This leads to significant lapses in adopting updated guidelines, variable decision making between physicians, and unnecessary screening for low to moderate risk patients (Jacobson and Kadiyala, 2017; Corbelli et al., 2014).For analysis, risk factors were assessed for patient screening behaviors and results. The outcome variable for the first analysis was whether the patient had undergone screening. The risk factors considered were age, marital status, education level, rural versus urban residence, and family history of breast cancer. The outcome variable for the second analysis was whether patients who had undergone breast cancer screening presented abnormal results. The risk factors considered were age, Body Mass Index, family history, smoking and alcohol status, hormonal contraceptive use, Hormone Replacement Therapy use, age of first pregnancy, number of pregnancies (parity), age of first menses, rural versus urban residence, and whether or not patients had at least one child.Logistic regression analysis displayed strong associations for both outcome variables. Risk of screening nonattendance was negatively associated with age as a continuous variable, age as a dichotomous variable, being married, any college education, and family history. Risk of one or more abnormal mammogram findings was positively associated with family history, and hormonal contraceptive use. This procedure will be further developed to incorporate additional risk factors and refine the analysis of currently implemented risk factors.

This paper presents an experimental study of a low-cost seismic isolator that can be used for the protection of residential structures in low-income countries. The isolator is based on mortar-filled, used tennis spheres, rolling on flat or spherical concrete surfaces. The tennis spheres serve as permanent, spherical molds to cast mortar, and they are not removed after casting. The thin rubber shell of the tennis sphere offers increased damping and reduces stress concentrations at the contact areas. At the same time, this procedure creates a promising solution for the re-use of tennis spheres. Using a closely-spaced grid of such spheres may allow for avoiding the diaphragm slab at the isolation level, or reducing its thickness. Avoiding the cost of this additional, heavily reinforced isolation slab is crucial for making seismically isolated low-rise dwellings economically feasible in low-income regions of the globe. Initially, the tennis isolators were subjected to monotonic uniaxial compression to examine their behavior under vertical loading. Different mixes and low-cost reinforcement approaches to increase their strength were tested. Subsequently, cyclic tests were performed to obtain the lateral force-displacement diagram of the isolation system. The effects of the geometry of the rolling surface (i.e., flat or concave) and of the applied compressive load (i.e., 2.08, 3.23, 4.74, or 8 kN/sphere) on the cyclic behavior were investigated. It was found that the restoring force of such systems mainly originates from the curvature of the concrete surface. However, the vertical motion induced by the compressed sphere and its local casting imperfections is not negligible. When surface imperfections become significant, the force-displacement loops deviate from the bilinear curves that a rigid-body model suggests. When the spheres are properly cast, they experience zero damage even under 8 kN of compressive force, and their loops have a bilinear form. For the tested configurations, the rolling friction (defined as the ratio of lateral to vertical force at zero displacement) was in the range of 4.7–7.2%, thus suitable for seismic isolation applications. The cost of the tested tennis ball isolators was 0.05 $ per sphere.

Objectives: To investigate the clinical characteristics, epidemiology, survival estimates and healthcare resource utilization and associated costs in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in France.Methods: The French national administrative healthcare database, the Système National des Données de Santé (SNDS), includes data on 98.8% of the French population, including data relating to ambulatory care, hospitalizations and death. In our study, claims data from the SNDS were used to identify adult patients with SSc-ILD between 2010 and 2017. We collected data on clinical features, incidence, prevalence, survival estimates, healthcare resource use and costs.Results: In total, 3,333 patients with SSc-ILD were identified, 76% of whom were female. Patients had a mean age [standard deviation (SD)] of 60.6 (14.4) years and a mean (SD) individual study duration of 3.9 (2.7) years. In 2016, the estimated overall incidence and prevalence were 0.69/100,000 individuals and 5.70/100,000 individuals, respectively. The overall survival estimates of patients using Kaplan–Meier estimation were 93, 82, and 55% at 1, 3, and 8 years, respectively. During the study, 98.7% of patients had ≥1 hospitalization and 22.3% of patients were hospitalized in an intensive care unit. The total annual mean healthcare cost per patient with SSc-ILD was €25,753, of which €21,539 was related to hospitalizations.Conclusions: This large, real-world longitudinal study provides important insights into the epidemiology of SSc-ILD in France and shows that the disease is associated with high mortality, healthcare resource utilization and costs. SSc-ILD represents a high burden on both patients and healthcare services.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03858842.

Using a risk-based approach, the SAGIR network (dedicated to wildlife disease surveillance) had to strengthen surveillance activities after ASF was confirmed in Belgium in September 2018, very near the French border. Three new active dead wild boars search protocols supplemented opportunistic surveillance in Level III risk areas: patrols by volunteer hunters, professional systematic combing, and dog detection. Those protocols were targeted in terms of location and time and complemented each other. The main objectives of the designed surveillance system were (i) to assure early detection in case of introduction of the disease and (ii) to support the free status of the zone. Compiling the surveillance effort was thus a necessity to assure authorities and producer representatives that the sometimes low number of carcasses detected was not a consequence of no surveillance activities. The human involvement in implementing those activities was significant: more than 1000 8-h days just for the time spent in the field on active search activities. We calculated a specific indicator to enable a comparison of the surveillance results from different zones, including non-infected Belgian zones with strengthened surveillance activities. This was a first step in the evaluation of the efficacy of our surveillance activities in a WB population. Field experiments and modelling dead WB detection probability are planned to supplement this evaluation. Belgium regained its ASF-free status in November 2020, and ASF was not detected in France in either the WB or domestic pig populations.

Abstract Purpose To assess the incidence of BCR‐ABL kinase domain (KD) mutation detection and its prognostic significance in chronic phase chronic myeloid leukemia (CP‐CML) patients treated with tyrosine kinase inhibitors (TKIs). Patients and Methods We analyzed characteristics and outcome of 253 CP‐CML patients who had at least one mutation analysis performed using direct sequencing. Of them, 187 patients were early CP (ECP) and 66 were late CP late chronic phase (LCP) and 88% were treated with Imatinib as first‐line TKI. Results Overall, 80 (32%) patients harbored BCR‐ABL KD mutations. A BCR‐ABL KD mutation was identified in 57% of patients, who progressed to accelerated or blastic phases (AP‐BP), and 47%, 29%, 35%, 16% and 26% in patients in CP‐CML at the time of mutation analysis who lost a complete hematologic response, failed to achieve or loss of a prior complete cytogenetic and major molecular response, respectively. Overall survival and cumulative incidence of CML‐related death were significantly correlated with the disease phase whatever the absence or presence of a mutation was and for the latter the mutation subgroup (T315I vs P‐loop vs non‐T315I non‐P‐loop) (P

Summary:. Arterialized venous flow-through flaps are solely vascularized through the venous plexus. The flaps were first described 40 years ago; however, reports of venous congestion and ischemia discouraged surgeons from adopting them into their armamentarium. Nevertheless, recent studies have demonstrated a resurgence of venous flow-through flaps for reconstruction of small to medium defects of the hand and digits. Although current data report variable levels of success in adults, no case reports have been published in the pediatric population for this type of flap. In this study, an arterialized venous flow-through flap from the medial forearm was used to reconstruct a volar hand defect in a young child. Flap markings, surgical technique, and aftercare are described. The surgery was uncomplicated, and the postoperative outcomes were aesthetically and functionally excellent. Venous flow-through flaps restore full-thickness defects, are relatively easy to perform, allow an early return to daily activities, and have almost no morbidity. These flaps offer excellent options for pediatric hand and finger defects.

Background:. Facial transplantation (FT) is recognized as the ultimate reconstruction for severely disfigured patients. The substantial cost of these procedures in a nationalized health system has not been extensively published. The first Canadian FT performed in May 2018 was a great opportunity to address this subject and evaluate the viability of such a program. Methods:. A detailed patient chart review was performed and a cost per unit approach was used to estimate the procedure cost. The preoperative, operative, and the postoperative periods up to 1-year after the surgery were analyzed. Financial support from private sponsors and Hospital Fund donations were considered. The literature on international FT and national solid organ transplantation was reviewed. Results:. The overall 1-year cost was estimated at $440,224 (2018 CAD). The costs are explained by a long hospital length of stay, costly immunosuppressive therapy, and high immunosuppression-related complications. Those findings are consistent with international FT literature. The societal impact of the surgery was minimized with a $36,921 (2018 CAD) grant obtained from an external contributor. Interestingly, the hospital foundation sustained a 794% increase in donations ($1,787,148; 2019 CAD) the year following the surgery. Conclusion:. Our experience confirmed that the combination of private funding, with positive goodwill and hospital donations, is a workable model for innovative surgery in the setting of a nationalized health system with financial restrictions.

Cette étude a pour objectif de montrer en quoi la pratique vidéoludique sur un jeu de rôle en ligne massivement multijoueurs (MMORPG) permet aux joueurs de développer des soft skills. Après une revue de la littérature sur la notion de soft skills et de leurs liens avec les MMORPG, l’étude empirique se porte sur le jeu Final Fantasy XIV pour sa récence et sa communauté dynamique. Pour mener à bien l’étude, des récits sont recueillis via un questionnaire auprès de 118 joueurs. Les résultats de l’analyse thématique manuelle, et lexicale automatique effectuée via le logiciel TROPES v8.5, montrent que les joueurs déclarent développer des soft skills dans leur pratique de jeu via les interactions sociales vécues. Le contexte du jeu conditionne le développement de ces softs skills qui prennent leur sens en fonction des situations en jeu. Le principal apport de cette recherche se trouve dans la prise en considération de ces softs skills par les joueurs comme pratique de serious-gaming. Les limites méthodologiques et éthiques évoquées sont autant de perspectives de recherches futures, qui permettent de montrer un lien étroit entre la pratique d’un MMORPG et l’acquisition de soft skills par les joueurs.

Background Whole exome sequencing and RNA sequencing (WES/RNASeq) should now be implemented in the clinical practice in order to increase access to optimal care for cancer patients. Providing results to Tumour Boards in a relevant time frame—that is, compatible with the clinical pathway—is crucial. Assessing the feasibility of this implementation in the French care system is the primary objective of the Multipli study, as one of the four pilot projects of the national France Genomic Medicine 2025 (FGM 2025) plan. The Multipli study encompasses two innovative trials which will be driven in around 2400 patients suffering from a soft-tissue sarcoma (Multisarc) or a metastatic colorectal carcinoma (Acompli).Methods Prior to launching the FGM 2025 cancer pilot study itself, the performance of the Multipli genomic workflow has been evaluated through each step, from the samples collection to the Molecular Tumour Board (MTB) report. Two Multipli-assigned INCa-labelled molecular genetics centres, the CEA-CNRGH sequencing platform and the Institut Bergonié’s Bioinformatics Platform were involved in a multicentric study. The duration of each step of the genomic workflow was monitored and bottlenecks were identified.Results Thirty barriers which could affect the quality of the samples, sequencing results and the duration of each step of the genomic pathway were identified and mastered. The global turnaround time from the sample reception to the MTB report was of 44 calendar days.Conclusion Our results demonstrate the feasibility of tumour genomic analysis by WES/RNASeq within a time frame compatible with the current cancer patient care. Lessons learnt from the Multipli WES/RNASeq Platforms Workflow Study will constitute guidelines for the forthcoming Multipli study and more broadly for the future clinical routine practice in the first two France Genomic Medicine 2025 platforms.

Intracellular microcolonies of bacteria (IMC), in some cases developing large extracellular cysts (bacterial aggregates), infecting primarily gill and digestive gland, have been historically reported in a wide diversity of economically important mollusk species worldwide, sometimes associated with severe lesions and mass mortality events. As an effort to characterize those organisms, traditionally named as Rickettsia or Chlamydia-like organisms, 1950 specimens comprising 22 mollusk species were collected over 10 countries and after histology examination, a selection of 99 samples involving 20 species were subjected to 16S rRNA gene amplicon sequencing. Phylogenetic analysis showed Endozoicomonadaceae sequences in all the mollusk species analyzed. Geographical differences in the distribution of Operational Taxonomic Units (OTUs) and a particular OTU associated with pathology in king scallop (OTU_2) were observed. The presence of Endozoicomonadaceae sequences in the IMC was visually confirmed by in situ hybridization (ISH) in eight selected samples. Sequencing data also indicated other symbiotic bacteria. Subsequent phylogenetic analysis of those OTUs revealed a novel microbial diversity associated with molluskan IMC infection distributed among different taxa, including the phylum Spirochetes, the families Anaplasmataceae and Simkaniaceae, the genera Mycoplasma and Francisella, and sulfur-oxidizing endosymbionts. Sequences like Francisella halioticida/philomiragia and Candidatus Brownia rhizoecola were also obtained, however, in the absence of ISH studies, the association between those organisms and the IMCs were not confirmed. The sequences identified in this study will allow for further molecular characterization of the microbial community associated with IMC infection in marine mollusks and their correlation with severity of the lesions to clarify their role as endosymbionts, commensals or true pathogens.