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Airway epithelial cells form a physical barrier against inhaled pathogens and coordinate innate immune responses in the lungs. Bronchial cells in people with cystic fibrosis (pwCF) are colonized by Pseudomonas aeruginosa because of the accumulation of mucus in the lower airways and an altered immune response. This leads to chronic inflammation, lung tissue damage, and accelerated decline in lung function. Thus, identifying the molecular factors involved in the host response in the airways is crucial for developing new therapeutic strategies. The septin (SEPT) cytoskeleton is involved in tissue barrier integrity and anti-infective responses. SEPT7 is critical for maintaining SEPT complexes and for sensing pathogenic microbes. In the lungs, SEPT7 may be involved in the epithelial barrier resistance to infection; however, its role in cystic fibrosis (CF) P. aeruginosa infection is unknown. This study aimed to investigate the role of SEPT7 in controlling P. aeruginosa infection in bronchial epithelial cells, particularly in CF. The study findings showed that SEPT7 encages P. aeruginosa in bronchial epithelial cells and its inhibition downregulates the expression of other SEPTs. In addition, P. aeruginosa does not regulate SEPT7 expression. Finally, we found that inhibiting SEPT7 expression in bronchial epithelial cells (BEAS-2B 16HBE14o- and primary cells) resulted in higher levels of internalized P. aeruginosa and decreased IL-6 production during infection, suggesting a crucial role of SEPT7 in the host response against this bacterium. However, these effects were not observed in the CF cells (16HBE14o-/F508del and primary cells) which may explain the persistence of infection in pwCF. The study findings suggest the modification of SEPT7 expression as a potential approach for the anti-infective control of P. aeruginosa, particularly in CF.

Non-Hodgkin lymphomas (NHL) commonly occur in immune-deficient (ID) patients, both HIV-infected and transplanted, and are often EBV-driven with cerebral localization, raising the question of tumor immunogenicity, a critical issue for treatment responses. We investigated the immunogenomics of 68 lymphoproliferative disorders from 51 ID (34 posttransplant, 17 HIV+) and 17 immunocompetent patients. Overall, 72% were Large B Cells Lymphoma (LBCL) and 25% were primary central-nervous-system lymphoma (PCNSL) while 40% were EBV-positive. Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline allowed analysis of tumor mutational burden (TMB), tumor landscape and microenvironment (TME) and prediction of tumor neoepitopes. Both TMB (2.2 vs 3.4/Mb, p=0.001) and neoepitopes numbers (40 vs 200, p=0.00019) were lower in EBVpositive than in EBV-negative NHL, regardless of the immune status. In contrast both EBV and the immune status influenced the tumor mutational profile, with HNRNPF and STAT3 mutations exclusively observed in EBV-positive and ID NHL, respectively. Peripheral blood T-cell responses against tumor neoepitopes were detected in all EBV-negative cases but in only half EBV-positive ones, including responses against IgH-derived MHC-class-II restricted neoepitopes. The TME analysis showed higher CD8 T cell infiltrates in EBVpositive vs EBV-negative NHL, together with a more tolerogenic profile composed of Tregs, type-M2 macrophages and an increased expression of negative immune-regulators. Our results highlight that the immunogenomics of NHL in patients with immunodeficiency primarily relies on the tumor EBV status, while T cell recognition of tumor- and IgH-specific neoepitopes is conserved in EBV-negative patients, offering potential opportunities for future T cell-based immune therapies.

La base de données du registre de dialyse péritonéale de langue française (RDPLF) est constituée de plusieurs modules spécialisés et interconnectés. Depuis 1980, les centres du RDPLF ont enregistré les principaux aspects de la formation infirmière, pour plus de 16.000 patients, dans un module infirmier destiné aux équipes soignantes. Nous rapportons une analyse descriptive des informations incluses dans le module infirmier du RDPLF sur les deux années 2022 et 2023, afin d’éviter le biais qui aurait pu être présent pendant la période de pandémie de SRAS Cov2 qui a précédé. Afin d’avoir une population homogène, nous n’avons inclus que des patients de France métropolitaine. L’âge moyen des patients était de 69,5±16 ans. Il était plus élevé en dialyse péritonéale continue ambulatoire (69,7 ans) qu’en dialyse péritonéale automatisée (DPA) (57,8 ans). Les patients autonomes représentaient 60% de la population étudiée. La majorité des patients savaient adapter leurs fluides à leur état clinique. Une modification des informations enregistrées dans le module sera nécessaire pour l’adapter aux outils de formation modernes.

Objectives Develop the Markov Index Load State (MILS) model, based on hidden Markov chains, to assess athletes’ workload responses and investigate the effects of menstrual cycle (MC)/oral contraception (OC), sex steroids hormones and wellness on elite athletes’ training.Methods On a 7-month longitudinal follow-up, daily training (volume and perceived effort, n=2200) and wellness (reported sleep quality and quantity, fitness, mood, menstrual symptoms, n=2509) data were collected from 24 female rowers and skiers preparing for the Olympics. 51 MC and 54 OC full cycles relying on 214 salivary hormone samples were analysed. MC/OC cycles were normalised, converted in % from 0% (first bleeding/pill withdrawal day) to 100% (end).Results MILS identified three chronic workload response states: ‘easy’, ‘moderate’ and ‘hard’. A cyclic training response linked to MC or OC (95% CI) was observed, primarily related to progesterone level (p=8.23e-03 and 5.72e-03 for the easy and hard state, respectively). MC athletes predominantly exhibited the ‘easy’ state during the cycle’s first half (8%–53%), transitioning to the ‘hard’ state post-estimated ovulation (63%–96%). OC users had an increased ‘hard’ state (4%–32%) during pill withdrawal, transitioning to ‘easy’ (50%–60%) when on the pill. Wellness metrics influenced the training load response: better sleep quality (p=5.20e-04), mood (p=8.94e-06) and fitness (p=6.29e-03) increased the likelihood of the ‘easy’ state. Menstrual symptoms increased the ‘hard’ state probability (p=5.92e-02).Conclusion The MILS model, leveraging hidden Markov chains, effectively analyses cumulative training load responses. The model identified cyclic training responses linked to MC/OC in elite female athletes.

BackgroundMajor advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy.MethodsA systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT.ResultsDespite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap–tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications.ConclusionFlap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.

The observational characterization of anthropogenic methane (CH4) emissions in the Eastern Mediterranean and Middle East (EMME) region, known for its significant oil and gas (OG) production, remains limited. Light alkanes, such as ethane (C2H6), are co-emitted with CH4 by OG activities and are promising tracers for identifying the CH4 emissions from this sector at the wider regional scale. In this study, in-situ measurements of CH4 and alkanes (C2–C8 were collected during a field campaign at a regional background site (Cape Greco, Cyprus). A mobile laboratory housed the instrumentation at the south-eastern edge of the island between December 2021 and February 2022. This specific location and time of year were selected to capture air masses originating from distant southern and eastern regions, primarily impacted by sources from the Middle East. Based on these observations we 1) evaluate the significance of long-range transported versus local sources in Cyprus, 2) identify and document regional anthropogenic CH4 sources with the help of the concomitant alkane measurements, and 3) assess the accuracy of the EDGAR sectoral emission inventory over the EMME region. The highest alkane mixing ratios observed were associated with the Middle Eastern OG CH4 signal. Surprisingly, the Middle Eastern emissions of CH4 were found to be heavily influenced by the breeding and waste management sectors. By investigating the measured CH4 mixing ratios together with an atmospheric dispersion model (FLEXPART), we derive a comprehensive characterization of the pollution sources at a regional scale over the Eastern Mediterranean region. Our results indicate that CH4 emissions from the Middle Eastern OG sector are likely underestimated by ca. 69 %. These findings underscore the efficacy of using experimental observations of alkanes for CH4 source identification at receptor sites. This tracer approach would also benefit from a substantial revision of light hydrocarbon emission inventories.

BackgroundThe infant mortality rate (IMR) serves as a key indicator of population health.MethodsWe used data from the French National Institute of Statistics and Economic Studies on births and deaths during the first year of life from 2001 to 2019 to calculate IMR aggregated by month. We ran joinpoint regressions to identify inflection points and assess the linear trend of each segment. Exploratory analyses were performed for overall IMR, as well as by age at death subgroups (early neonatal [D0-D6], late neonatal [D7-27], and post-neonatal [D28-364]), and by sex. We performed sensitivity analyses by excluding deaths at D0 and using other time-series modeling strategies.ResultsOver the 19-year study period, 53,077 infant deaths occurred, for an average IMR of 3·63/1000 (4·00 in male, 3·25 in female); 24·4% of these deaths occurred during the first day of life and 47·8% during the early neonatal period. Joinpoint analysis identified two inflection points in 2005 and 2012. The IMR decreased sharply from 2001 to 2005 (slope: -0·0167 deaths/1000 live births/month; 95%CI: -0·0219 to -0·0116) and then decreased slowly between 2005 and 2012 (slope: -0·0041; 95%CI: -0·0065 to -0·0016). From 2012 onwards, a significant increase in IMR was observed (slope: 0·0033; 95%CI: 0·0011 to 0·0056). Subgroup analyses indicated that these trends were driven notably by an increase in the early neonatal period. Sensitivity analyses provided consistent results.InterpretationThe recent historic increase in IMR since 2012 in France should prompt urgent in-depth investigation to understand the causes and prepare corrective actions.FundingNo financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Pulmonary functional imaging has demonstrated potential to improve thoracic radiotherapy. The purpose of this study was twofold: 1) to quantify ventilation/perfusion relationships in lung cancer patients using a new functional imaging approach, gallium-68 (68Ga)-positron emission tomography/computed tomography (PET/CT); and 2) to compare ventilation/perfusion matching with diffusing capacity of the lung for carbon monoxide (DLCO). Voxel-wise correlations between ventilation and perfusion varied widely among 19 patients (range: 0.26-0.88). 68Ga-PET/CT-measured percent gas exchanging lung volume was moderately correlated with DLCO (≤0.59). Our findings suggested that 68Ga-PET/CT ventilation/perfusion imaging provided complementary information and a reasonable surrogate for gas exchange in lung cancer patients.

Abstract An in situ microscope based on pulsed transmitted light illumination via optical fiber was combined to artificial-intelligence to enable for the first time an online cell classification according to well-known cellular morphological features. A 848 192-image database generated during a lab-scale production process of antibodies was processed using a convolutional neural network approach chosen for its accurate real-time object detection capabilities. In order to induce different cell death routes, hybridomas were grown in normal or suboptimal conditions in a stirred tank reactor, in the presence of substrate limitation, medium addition, pH regulation problem or oxygen depletion. Using such an optical system made it possible to monitor real-time the evolution of different classes of animal cells, among which viable, necrotic and apoptotic cells. A class of viable cells displaying bulges in feast or famine conditions was also revealed. Considered as a breakthrough in the catalogue of process analytical tools, in situ microscopy powered by artificial-intelligence is also of great interest for research.

Abstract Background The aim was to investigate the feasibility of a shortened dynamic whole-body (dWB) FDG-PET/CT protocol and Patlak imaging using a population-based input function (PBIF), instead of an image-derived input function (IDIF) across the 60-min post-injection period, and study its effect on the FDG influx rate (Ki) quantification in patients with metastatic melanoma (MM) undergoing immunotherapy. Methods Thirty-seven patients were enrolled, including a PBIF modeling group (n = 17) and an independent validation cohort (n = 20) of MM from the ongoing prospective IMMUNOPET2 trial. All dWB-PET data were acquired on Vision 600 PET/CT systems. The PBIF was fitted using a Feng’s 4-compartments model and scaled to the individual IDIF tail’s section within the shortened acquisition time. The area under the curve (AUC) of PBIFs was compared to respective IDIFs AUC within 9 shortened time windows (TW) in terms of linear correlation (R 2) and Bland–Altman tests. Ki metrics calculated with PBIF vs IDIF on 8 organs with physiological tracer uptake, 44 tumoral lesions of MM and 11 immune-induced inflammatory sites of pseudo-progression disease were also compared (Mann–Whitney test). Results The mean ± SD relative AUC bias was calculated at 0.5 ± 3.8% (R 2 = 0.961, AUCPBIF = 1.007 × AUCIDIF). In terms of optimal use in routine practice and statistical results, the 5th–7th pass (R 2 = 0.999 for both Ki mean and Ki max) and 5th–8th pass (mean ± SD bias = − 4.9 ± 6.5% for Ki mean and − 4.8% ± 5.6% for Ki max) windows were selected. There was no significant difference in Ki values from PBIF5_7 vs IDIF5_7 for physiological uptakes (p > 0.05) as well as for tumor lesions (mean ± SD Ki IDIF5_7 3.07 ± 3.27 vs Ki PBIF5_7 2.86 ± 2.96 100ml/ml/min, p = 0.586) and for inflammatory sites (mean ± SD Ki IDIF5_7 1.13 ± 0.59 vs Ki PBIF5_7 1.13 ± 0.55 100ml/ml/min, p = 0.98). Conclusion Our study showed the feasibility of a shortened dWB-PET imaging protocol with a PBIF approach, allowing to reduce acquisition duration from 70 to 20 min with reasonable bias. These findings open perspectives for its clinical use in routine practice such as treatment response assessment in oncology.

Flow and spontaneous imbibition phenomena in porous media are important for various industrial applications, including printing and medical lateral flow assays. Their quantitative characterization is important to better understand and select the appropriate raw materials. However, standard methods often require time-consuming tests, and/or expensive equipment. Different time scales must be considered, limiting the range of possible characterization tools. A novel experimental approach based on image analysis for characterizing spontaneous imbibition processes is presented. Hence, ultra-fast diffusion may be quantitatively characterized. Models are issued from the literature to consider physical phenomena at small (milliseconds) and medium range (seconds) of time scales. The obtained experimental data fit with theoretical results, providing valuable insights into the understanding of fluid flow behavior at different time scales. Furthermore, the identification of some physical properties for either the fluid, or the substrate, based on the theoretical models are possible, as the contact angle, which remains to be otherwise challenging. This study contributes to bridging the gap between spontaneous imbibition and capillary phenomena at different time scales, their modeling, and a characterization of material and/or fluid properties paving the way for enhanced understanding and control of fluid behavior in porous media. Different papers are considered to illustrate the method.

There are approximately 1.5 billion specimens kept in European Natural History Collections. The mission for the Distributed System of Scientific Collections (DiSSCo) is to unite all these specimens into a one-stop e-science infrastructure of digital specimens. This is a monumental digitisation task and criteria for how to prioritise this effort are, therefore, crucial for the success of the project. In this report, we have reviewed the literature and designed and conducted surveys of the digitisation plans and criteria used by DiSSCo Partners to understand the prioritisation criteria used in the digitisation of natural history collections. As an attempt to provide some guidance for the digitisation of specimens, we suggest that an organisation (e.g. DiSSCo or an individual institution) that is planning to digitise natural history collections considers four categories of prioritisation criteria: Relevance, Data quality, Cost and Feasibility.

Abstract Background Inter-facility transport of patients with acute respiratory distress syndrome (ARDS) in the prone position (PP) is a high-risk situation, compared to other strategies. We aimed to quantify the prevalence of complications during transport in PP, compared to transports with veno-venous extracorporeal membrane oxygenation (VV-ECMO) or in the supine position (SP). Methods We performed a retrospective, single center cohort study in Lyon university hospital, France. We included patients ≥ 16 years with ARDS (Berlin definition) transported to an ARDS referral center between 01/12/2016 and 31/12/2021. We compared patients transported in PP, to those transported in SP without VV-ECMO, and those transported with VV-ECMO (in SP), by a multidisciplinary and specialized medical transport team, including an emergency physician and an intensivist. The primary outcome was the rate of transport-related complications (hypoxemia, hypotension, cardiac arrest, cannula or tube dislodgement) in each study groups, compared using a Fisher test. Results One hundred thirty-four patients were enrolled (median PaO2/FiO2 70 [58–82] mmHg), of which 11 (8%) were transported in PP, 44 (33%) with VV-ECMO, and 79 (59%) in SP. The most frequent risk factor for ARDS in the PP group was bacterial pneumonitis, and viral pneumonitis in the other 2 groups. Transport-related complications occurred in 36% (n = 4) of transports in PP, compared to 39% (n = 30) in SP and 14% (n = 6) with VV-ECMO, respectively (p = 0.33). VV-ECMO implantation after transport was not different between SP and PP patients (n = 7, 64% vs. n = 31, 39%, p = 0.19). Conclusions In the context of a specialized multi-disciplinary ARDS transport team, transport-related complication rates were similar between patients transported in PP and SP, while there was a trend of lower rates in patients transported with VV-ECMO.

Tens of millions of images from biological collections have become available online over the last two decades. In parallel, there has been a dramatic increase in the capabilities of image analysis technologies, especially those involving machine learning and computer vision. While image analysis has become mainstream in consumer applications, it is still used only on an artisanal basis in the biological collections community, largely because the image corpora are dispersed. Yet, there is massive untapped potential for novel applications and research if images of collection objects could be made accessible in a single corpus. In this paper, we make the case for infrastructure that could support image analysis of collection objects. We show that such infrastructure is entirely feasible and well worth investing in.

Abstract For successful infection of host cells and virion production, enveloped viruses, including Zika virus (ZIKV), extensively rely on cellular lipids. However, how virus protein–lipid interactions contribute to the viral life cycle remains unclear. Here, we employ a chemo-proteomics approach with a bifunctional cholesterol probe and show that cholesterol is closely associated with the ZIKV structural protein prM. Bioinformatic analyses, reverse genetics alongside with photoaffinity labeling assays, and atomistic molecular dynamics simulations identified two functional cholesterol binding motifs within the prM transmembrane domain. Loss of prM–cholesterol association has a bipartite effect reducing ZIKV entry and leading to assembly defects. We propose a model in which membrane-resident M facilitates cholesterol-supported lipid exchange during endosomal entry and, together with cholesterol, creates a platform promoting virion assembly. In summary, we identify a bifunctional role of prM in the ZIKV life cycle by mediating viral entry and virus assembly in a cholesterol-dependent manner.

We report a rare clinical case of infection with the bacterium Sphingobium yanoikuyae in an 87-year-old patient undergoing peritoneal dialysis for end-stage renal failure. Sphingobium yanoikuyae is an aerobic, gram-negative bacterium known for its ability to degrade polycyclic aromatic hydrocarbons and its bioremediation potential. A member of the Sphingomonadaceae family, it has been identified in a variety of environments, including dialysis equipment. After starting peritoneal dialysis, the patient developed an infectious syndrome. Bacteriological analysis of the peritoneal effluent revealed the presence of Sphingobium yanoikuyae in the dialysate. Appropriate antibiotic therapy with MEROPENEM was instituted as soon as the Sphyngobium antibiogram was obtained. A second bacterium, Shingomonas sp, was also identified later (resistant to MEROPENEM). Due to the favorable clinicobiological course, only Sphyngobium was considered responsible for the disease. This is the first known case of human infection with Sphingobium yanoikuyae, and the third case of infection with a Sphingobium species in a peritoneal dialysis setting. The low prevalence of this germ in human infections suggests a low virulence of this bacterium. Nevertheless, this highlights the potential risk of nosocomial infections linked to this family of bacteria. This germ has shown antibiotic resistance, raising concerns about anti-infective resistance in opportunistic bacteria such as Sphingomonadaceae. This case adds to our knowledge of rare, antibiotic-resistant infections in the hospital setting, particularly in vulnerable patients treated with peritoneal dialysis.

Campylobacter fetus accounts for 1% of Campylobacter spp. infections, but prevalence of bacteremia and risk for death are high. To determine clinical features of C. fetus infections and risks for death, we conducted a retrospective observational study of all adult inpatients with a confirmed C. fetus infection in Nord Franche-Comté Hospital, Trevenans, France, during January 2000–December 2021. Among 991 patients with isolated Campylobacter spp. strains, we identified 39 (4%) with culture-positive C. fetus infections, of which 33 had complete records and underwent further analysis; 21 had documented bacteremia and 12 did not. Secondary localizations were reported for 7 (33%) patients with C. fetus bacteremia, of which 5 exhibited a predilection for vascular infections (including 3 with mycotic aneurysm). Another 7 (33%) patients with C. fetus bacteremia died within 30 days. Significant risk factors associated with death within 30 days were dyspnea, quick sequential organ failure assessment score >2 at admission, and septic shock.