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Purpose of Review: This review investigates the roles of artificial intelligence (AI) and virtual reality (VR) in enhancing cognitive pain therapy for chronic pain management. The work assesses current research, outlines benefits and limitations and examines their potential integration into existing pain management methods., Recent Findings: Advances in VR have shown promise in chronic pain management through immersive cognitive therapy exercises, with evidence supporting VR's effectiveness in symptom reduction. AI's personalization of treatment plans and its support for mental health through AI-driven avatars are emerging trends. The integration of AI in hybrid programs indicates a future with real-time adaptive technology tailored to individual needs in chronic pain management. Incorporating AI and VR into chronic pain cognitive therapy represents a promising approach to enhance management by leveraging VR's immersive experiences and AI's personalized tactics, aiming to improve patient engagement and outcomes. Nonetheless, further empirical studies are needed to standardized methodologies, compare these technologies to traditional therapies and fully realize their clinical potential., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A Gram-negative, strictly aerobic bacterial strain was isolated from asymptomatic leaf tissue of a wild yam plant. Optimal growth was observed at 28 °C and pH 7, and catalase and oxidase activities were detected. Polyphasic taxonomic and comparative genomics revealed that strain LMG 33091 T represents a novel species of Pseudomonas . The nearest phylogenetic neighbours of strain LMG 33091 T were Pseudomonas putida NBRC 14164 T (with 99.79 % 16S rRNA sequence identity), Pseudomonas alkylphenolica KL28 T (99.28 %) and Pseudomonas asplenii (99.07 %) ATCC 23835 T . MALDI-TOF MS analysis yielded distinct profiles for strain LMG 33091 T and the nearest phylogenetic neighbours. Average nucleotide identity analyses between the whole genome sequence of strain LMG 33091 T and of the type strains of its nearest-neighbour taxa yielded values below the species delineation threshold and thus confirmed that the strain represented a novel Pseudomonas species, for which we propose the name Pseudomonas fortuita sp. nov., with strain LMG 33091 T (=GMI12077 T = CFBP 9143 T ) as the type strain.

Objectives: To determine if a multidisciplinary institutional protocol can optimize the time to antibiotic (Abx) administration for open fractures (openFx) and improve compliance with the administration of Abx prophylaxis during trauma activation., Design: Retrospective pre-post study design., Setting: Single Level II Trauma Center., Patient Selection Criteria: All patients who triggered a trauma activation with suspected openFx and were treated according to the institutional single antibiotic regimen were eligible for inclusion. Patients were excluded if fractures did not involve the appendicular skeleton. Patients treated before implementation of a standardized institutional protocol where premixed IV bags of antibiotics were stocked in automated dispensing systems within ED trauma bays (January 2021-October 2022) were defined as the "pre" group and those treated following implementation the "post" group., Outcome Measures and Comparisons: The primary outcome was time from trauma bay arrival to antibiotic aministration, measured in minutes, with comparisons made between preprotocol and postprotocol implementation. Secondary outcomes for comparison included rates (%) of time to Abx <60 minutes, allergic reactions, acute kidney injury, ototoxicity, surgical site infection, multi-drug-resistant organisms identified in blood or biopsy cultures in cases requiring reoperation, and Clostridium difficile infection in the gastrointestinal system, confirmed by stool test results, within 30 days., Results: Twenty-four patients (mean age 39.5 ± 16.3 years) met the criteria after protocol implementation compared with 72 patients (mean age 34.3 ± 14.8 years) before implementation. Implementation of the institutional protocol resulted in a significant reduction in the time to Abx administration for openFx from 87.9 ± 104.6 minutes to 22.2 ± 12.8 minutes in the postprotocol group ( P < 0.001). In addition, only 53% in the preprotocol group received Abx within 60 minutes compared with 96% in postprotocol group ( P < 0.001). Post hoc power analysis revealed that the study was powered at 92% (effect size = 0.72) to detect a significant difference between the preprotocol and postprotocol groups., Conclusion: This study provides evidence that a multidisciplinary institutional protocol for the administration of Abx prophylaxis can be an effective strategy for optimizing the time to Abx administration in cases of suspected openFx. This protocol may be implemented in other trauma centers to optimize time to Abx administration for openFx., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Each author certifies that there are no funding or commercial associations that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We investigated using a custom NGS panel of 149 genes the mutational landscape of 64 consecutive adult patients with tyrosine kinase fusion-negative hypereosinophilia (HE)/hypereosinophilic syndrome (HES) harboring features suggestive of myeloid neoplasm. At least one mutation was reported in 50/64 (78%) patients (compared to 8/44 (18%) patients with idiopathic HE/HES/HE US used as controls; p < .001). Thirty-five patients (54%) had at least one mutation involving the JAK-STAT pathway, including STAT5B (n = 18, among which the hotspot N642H, n = 13), JAK1 (indels in exon 13, n = 5; V658F/L, n = 2), and JAK2 (V617F, n = 6; indels in exon 13, n = 2). Other previously undescribed somatic mutations were also found in JAK2, JAK1, STAT5B, and STAT5A, including three patients who shared the same STAT5A V707fs mutation and features consistent with primary polycythemia. Nearly all JAK-STAT mutations were preceded by (or associated with) myelodysplasia-related gene mutations, especially in RNA-splicing genes or chromatin modifiers. In multivariate analysis, neurologic involvement (hazard ratio [HR] 4.95 [1.87-13.13]; p = .001), anemia (HR 5.50 [2.24-13.49]; p < .001), and the presence of a high-risk mutation (as per the molecular international prognosis scoring system: HR 6.87 [2.39-19.72]; p < .001) were independently associated with impaired overall survival. While corticosteroids were ineffective in all treated JAK-STAT-mutated patients, ruxolitinib showed positive hematological responses including in STAT5A-mutated patients. These findings emphasize the usefulness of NGS for the workup of tyrosine kinase fusion-negative HE/HES patients and support the use of JAK inhibitors in this setting. Updated classifications could consider patients with JAK-STAT mutations and eosinophilia as a new "gene mutated-entity" that could be differentiated from CEL, NOS, and idiopathic HES., (© 2024 Wiley Periodicals LLC.)

Hereditary, or vertically-transmitted, symbioses affect a large number of animal species and some plants. The precise mechanisms underlying transmission of functions of these associations are often difficult to describe, due to the difficulty in separating the symbiotic partners. This is especially the case for plant-bacteria hereditary symbioses, which lack experimentally tractable model systems. Here, we demonstrate the potential of the leaf symbiosis between the wild yam Dioscorea sansibarensis and the bacterium Orrella dioscoreae (O. dioscoreae) as a model system for hereditary symbiosis. O. dioscoreae is easy to grow and genetically manipulate, which is unusual for hereditary symbionts. These properties allowed us to design an effective antimicrobial treatment to rid plants of bacteria and generate whole aposymbiotic plants, which can later be re-inoculated with bacterial cultures. Aposymbiotic plants did not differ morphologically from symbiotic plants and the leaf forerunner tip containing the symbiotic glands formed normally even in the absence of bacteria, but microscopic differences between symbiotic and aposymbiotic glands highlight the influence of bacteria on the development of trichomes and secretion of mucilage. This is to our knowledge the first leaf symbiosis where both host and symbiont can be grown separately and where the symbiont can be genetically altered and reintroduced to the host., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Acar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose of Review: This review critically analyzes the recent literature on virtual reality's (VR) use in acute and chronic pain management, offering insights into its efficacy, applications, and limitations., Recent Findings: Recent studies, including meta-analyses and randomized controlled trials, have demonstrated VR's effectiveness in reducing pain intensity in various acute pain scenarios, such as procedural/acute pain and in chronic pain conditions. The role of factors such as immersion and presence in enhancing VR's efficacy has been emphasized. Further benefits have been identified in the use of VR for assessment as well as symptom gathering through conversational avatars. However, studies are limited, and strong conclusions will require further investigation. VR is emerging as a promising non-pharmacological intervention in pain management for acute and chronic pain. However, its long-term efficacy, particularly in chronic pain management, remains an area requiring further research. Key findings highlight that VR programs vary in efficacy depending on the specificity of the origin of pain., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: This review provides medical practitioners with an overview of the present and emergent roles of telehealth and associated virtual reality (VR) applications in chronic pain (CP) management, particularly in the post-COVID-19 healthcare landscape., Recent Findings: Accumulated evidence points to the efficacy of now well-established telehealth modalities, such as videoconferencing, short messaging service (SMS), and mobile health (mHealth) applications in complementing remote CP care. More recently, and although still in early phases of clinical implementation, a wide range of VR-based interventions have demonstrated potential for improving the asynchronous remote management of CP. Additionally, VR-associated technologies at the leading edge of science and engineering, such as VR-assisted biofeedback, haptic technology, high-definition three-dimensional (HD3D) conferencing, VR-enabled interactions in a Metaverse, and the use of wearable monitoring devices, herald a new era for remote, synchronous patient-physician interactions. These advancements hold the potential to facilitate remote physical examinations, personalized remote care, and innovative interventions such as ultra-realistic biofeedback. Despite the promise of VR-associated technologies, several limitations remain, including the paucity of robust long-term effectiveness data, heterogeneity of reported pain-related outcomes, challenges with scalability and insurance coverage, and demographic-specific barriers to patient acceptability. Future research efforts should be directed toward mitigating these limitations to facilitate the integration of telehealth-associated VR into the conventional management of CP. Despite ongoing barriers to widespread adoption, recent evidence suggests that VR-based interventions hold an increasing potential to complement and enhance the remote delivery of CP care., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cellulose is the world's most abundant biopolymer, and similar to its role as a cell wall component in plants, it is a prevalent constituent of the extracellular matrix in bacterial biofilms. Although bacterial cellulose (BC) was first described in the 19 th century, it was only recently revealed that it is produced by several distinct types of Bcs secretion systems that feature multiple accessory subunits in addition to a catalytic BcsAB synthase tandem. We recently showed that crystalline cellulose secretion in the Gluconacetobacter genus (α-Proteobacteria) is driven by a supramolecular BcsH-BcsD scaffold-the "cortical belt"-which stabilizes the synthase nanoarrays through an unexpected inside-out mechanism for secretion system assembly. Interestingly, while bcsH is specific for Gluconacetobacter, bcsD homologs are widespread in Proteobacteria. Here, we examine BcsD homologs and their gene neighborhoods from several plant-colonizing β- and γ-Proteobacteria proposed to secrete a variety of non-crystalline and/or chemically modified cellulosic polymers. We provide structural and mechanistic evidence that through different quaternary structure assemblies BcsD acts with proline-rich BcsH, BcsP, or BcsO partners across the proteobacterial clade to form synthase-interacting intracellular scaffolds that, in turn, determine the biofilm strength and architecture in species with strikingly different physiology and secreted biopolymers., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The syntheses of novel 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinazolines 12 and 2,4-bis[(substituted-aminomethyl)phenyl]phenylquinolines 13 are reported here in six steps starting from various halogeno-quinazoline-2,4-(1 H ,3 H )-diones or substituted anilines. The antiproliferative activities of the products were determined in vitro against a panel of breast (MCF-7 and MDA-MB-231), human adherent cervical (HeLa and SiHa), and ovarian (A2780) cell lines. Disubstituted 6- and 7-phenyl-bis(3-dimethylaminopropyl)aminomethylphenyl-quinazolines 12b , 12f , and 12i displayed the most interesting antiproliferative activities against six human cancer cell lines. In the series of quinoline derivatives, 6-phenyl-bis(3-dimethylaminopropyl)aminomethylphenylquinoline 13a proved to be the most active. G-quadruplexes (G4) stacked non-canonical nucleic acid structures found in specific G-rich DNA, or RNA sequences in the human genome are considered as potential targets for the development of anticancer agents. Then, as small aza-organic heterocyclic derivatives are well known to target and stabilize G4 structures, their ability to bind G4 structures have been determined through FRET melting, circular dichroism, and native mass spectrometry assays. Finally, telomerase inhibition ability has been also assessed using the MCF-7 cell line.

Patients with cystic fibrosis (CF) exhibit pronounced respiratory damage and were initially considered among those at highest risk for serious harm from SARS-CoV-2 infection. Numerous clinical studies have subsequently reported that individuals with CF in North America and Europe-while susceptible to severe COVID-19-are often spared from the highest levels of virus-associated mortality. To understand features that might influence COVID-19 among patients with cystic fibrosis, we studied relationships between SARS-CoV-2 and the gene responsible for CF (i.e., the cystic fibrosis transmembrane conductance regulator, CFTR). In contrast to previous reports, we found no association between CFTR carrier status (mutation heterozygosity) and more severe COVID-19 clinical outcomes. We did observe an unexpected trend toward higher mortality among control individuals compared with silent carriers of the common F508del CFTR variant-a finding that will require further study. We next performed experiments to test the influence of homozygous CFTR deficiency on viral propagation and showed that SARS-CoV-2 production in primary airway cells was not altered by the absence of functional CFTR using two independent protocols. On the contrary, experiments performed in vitro strongly indicated that virus proliferation depended on features of the mucosal fluid layer known to be disrupted by absent CFTR in patients with CF, including both low pH and increased viscosity. These results point to the acidic, viscous, and mucus-obstructed airways in patients with cystic fibrosis as unfavorable for the establishment of coronaviral infection. Our findings provide new and important information concerning relationships between the CF clinical phenotype and severity of COVID-19., (© 2023 Federation of American Societies for Experimental Biology.)

Background: Patients with substance use disorders are often encountered in an acute care setting and withdrawal management is important. Available literature reveals inadequate acute management of substance withdrawal due to lack of experience and knowledge of medications., Methods: A quality improvement project was implemented to improve hospital pharmacists' knowledge, application, and practice of inpatient opioid and alcohol withdrawal management through provision of didactic and case-based education and implementation of practice based prospective drug utilization review (PDUR). Pharmacists' knowledge of the management of alcohol and opioid withdrawal was assessed by a 10-item survey pre-and post-intervention., Results: Twenty-one pharmacists completed the education and pre- and post-surveys. Scores for the 21 pharmacists improved significantly, with pre- and post-intervention scores of 7.33 ± 1.98 and 8.86 ± 0.91, respectively ( P  = .0035). Most pharmacists completed their required PDUR submission, and several pharmacist interventions were made and accepted post-education. Pharmacists indicated that the education increased their confidence and enabled them to learn new information that could be directly applied to their pharmacy practice., Conclusion: Providing education and requiring a PDUR improved pharmacists' knowledge, application, and practice of inpatient opioid and alcohol withdrawal management. Re-education or expanded education may be warranted to further increase pharmacists' competence., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Belantamab mafodotin (BM) is an anti-BCMA antibody-drug conjugate (GSK2857916) that represents an alternative option in multiple myeloma. We sought to assess the efficacy and safety of BM in a real-world setting in patients who benefited from an early access program. We conducted an observational, retrospective, multicenter study. Eligibility criteria were treatment of relapsed or refractory multiple myeloma (RRMM) in monotherapy in adult patients who have received at least three lines of therapy previously, including at least one immunomodulatory agent (IMiD), a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody, and whose disease progressed during the last treatment period. The primary endpoint of the study is to assess the overall survival (OS). Between November 2019 and December 2020, 106 patients were treated with BM; 97 were eligible for the efficacy evaluation and 104 for safety. The median age was 66 (range, 37-82) years. High-risk cytogenetics were identified in 40.9% of patients. Fifty-five (56.7%) patients were triple-class refractory and 11 (11.3%) were penta-class refractory. The median number of prior lines of treatment was five (range, 3-12). The median number of BM cycles administered was three (range, 1-22). The overall response rate at best response was 38.1% (37/97). The median OS was 9.3 months (95% confidence interval [CI]: 5.9-15.3), and median progression-free survival was 3.5 months (95% CI: 1.9-4.7). The median duration of response was 9 months (range, 4.65-10.4). Treatment was delayed for 55 (52.9%) patients including 36.5% for treatment-related toxicity. Ophthalmic adverse events, mainly grade ≤2, were the most common toxicity (48%). The occurrence of keratopathy was 37.5%. Overall, our data are concordant with the results from DREAMM-2 in terms of efficacy and safety on a non-biased population.

Lures and other adaptations for prey attraction are particularly interesting from an evolutionary viewpoint because they are characterized by correlational selection, involve multicomponent signals, and likely reflect a compromise between maximizing conspicuousness to prey while avoiding drawing attention of enemies and predators. Therefore, investigating the evolution of lure and prey-attraction adaptations can help us understand a larger set of traits governing interactions among organisms. We review the literature focusing on spiders (Araneae), which is the most diverse animal group using prey attraction and show that the evolution of prey-attraction strategies must be driven by a trade-off between foraging and predator avoidance. This is because increasing detectability by potential prey often also results in increased detectability by predators higher in the food chain. Thus increasing prey attraction must come at a cost of increased risk of predation. Given this trade-off, we should expect lures and other prey-attraction traits to remain suboptimal despite a potential to reach an optimal level of attractiveness. We argue that the presence of this trade-off and the multivariate nature of prey-attraction traits are two important mechanisms that might maintain the diversity of prey-attraction strategies within and between species. Overall, we aim to stimulate research on this topic and progress in our general understanding of the diversity of predator and prey interactions., (© 2023. The Author(s).)

Introduction: Elderly patients with haematological malignancies are a population at risk of iatrogenic for whom these activities could optimize therapeutic management. However, the limitation of human resources requires optimization of the process in order to improve the efficiency of pharmaceutical activities. The objective was to build a decision tree to optimize the pharmaceutical consultation in these population within a multidisciplinary team in haematology., Method: Pharmaceutical consultations were proposed to elderly subjects with haematological malignancies followed up in a haematology day hospitalization at the University Hospital of Limoges. Risk factors for prescribing risky drugs in this population were determined by logistic regression models. A decision tree was constructed based on these results and by agreement between pharmacist, geriatrician and hematologist., Results: Female gender (aOR[CI95%] = 1.71 [1.14-2.57]), polypharmacy (aOR[CI95%] = 1.89 [1.14-3.13]), hyper-polypharmacy (aOR[CI95%] = 5.73 [3.03-10.84]) and moderate cholinergic load (aOR[CI95%] = 2.15 [1.04-4.45]) were risk factors for the prescription of inappropriate medicine. Female gender (aOR[CI95%] = 1.55 [1.02-2.35]) and hyper-polypharmacy (aOR[CI95%] = 6.19 [1-1.28]) were risk factors for prescribing anticholinergic drugs or anticoagulants; in contrast, frailty status was a protective factor for prescribing anticholinergics (aOR[CI95%] = 0.51 [0.33-0.81]). Prioritization of pharmaceutical consultations is based on frailty status, prescription of a target drug and polypharmacy., Discussion: Pharmaceutical consultations during the day hospitalization of elderly subjects with hematological diseases allow to propose therapeutic optimizations. The prioritization proposed in our study would increase the efficiency of pharmaceutical activities in order to improve quality and safety throughout the care pathway of these patients.

The Southern Ocean is a major sink of anthropogenic CO 2 and an important foraging area for top trophic level consumers. However, iron limitation sets an upper limit to primary productivity. Here we report on a considerably dense late summer phytoplankton bloom spanning 9000 km 2 in the open ocean of the eastern Weddell Gyre. Over its 2.5 months duration, the bloom accumulated up to 20 g C m -2 of organic matter, which is unusually high for Southern Ocean open waters. We show that, over 1997-2019, this open ocean bloom was likely driven by anomalies in easterly winds that push sea ice southwards and favor the upwelling of Warm Deep Water enriched in hydrothermal iron and, possibly, other iron sources. This recurring open ocean bloom likely facilitates enhanced carbon export and sustains high standing stocks of Antarctic krill, supporting feeding hot spots for marine birds and baleen whales., (© 2023. The Author(s).)

Managing risk for aspiration in the stroke patient will assist to decrease one of the major complications that these patients experience, which is poststroke pneumonia. Using an evidenced-based dysphagia protocol is shown to reduce mortality, morbidity, and length of stay caused by poststroke pneumonia. Physicians, nurses, speech pathologists, and dieticians will be instrumental in performing ongoing assessments and aspiration-prevention strategies to improve stroke patient outcome and reduce complications. Education, and measurement of comprehension, of the care team, patient, and family concerning dysphagia management and prevention of aspiration pneumonia will assist in achieving the aforementioned goals., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Conservative treatments including bracing and exercise therapy are prescribed on the first-line in adults with degenerative scoliosis. However, adherence to conservative treatments is low. We aimed to assess barriers and facilitators to bracing in adults with painful degenerative scoliosis., Methods: We conducted a single-centred mixed-method pilot and feasibility study. All patients scheduled for a multidisciplinary custom-made bracing consultation, from July 2019 to January 2020, in a French tertiary care centre, were screened. Patients were eligible if they had painful adult degenerative scoliosis and a prescription for a rigid custom-made lumbar-sacral orthosis. The primary outcome was barriers and facilitators to bracing assessed by a qualitative approach using semi-structured interviews. Secondary outcomes were back pain, spine-specific activity limitations, symptoms of depression and satisfaction with bracing post-intervention assessed by a quantitative approach., Results: Overall, 56 patients were screened and 14 (25%) were included. Mean age was 68.2 (12.3) years. Mean follow-up was 9.8 (2.0) months. Barriers to bracing were increased limitations in some activities, discomfort in hot weather and burden of aesthetic appearance. Facilitators to bracing were reduced pain, improved activities of daily living, suitable weight and improved spinal alignment. Participants self-implemented solutions to enhance adherence. The mean reduction from baseline in pain intensity was 1.7 (2.3) of 10 points, and 6 of 13 patients (46%) had pain intensity < 4 of 10 points., Conclusion: Bracing is a feasible intervention for people with painful adult degenerative scoliosis. Patients self-implemented their own solutions to enhance adherence., (© 2023. The Author(s).)

The infiltration of secondary treated effluent (STE) into the soil downstream of wastewater treatment plants is becoming increasingly common in a climate change context. In STE infiltration, STE is discharged onto the soil over a large surface allowing for a gradual infiltration of the water. This paper investigates a novel time-lapse electrical resistivity tomography strategy to evaluate the impact of STE infiltration on the water pathways of two planted loamy-soil trenches located in a Fluvisol region in southwestern France. The system has been monitored for 3 years using discontinuous monitoring of electrical resistivity tomography during four saline tracer tests. Results show that: 1) the new methodology has successfully highlighted the evolution of water pathways in the soil over time; 2) such evolution is in agreement with reeds root distribution in the trenches which seems to be affected by water quality i.e. sludge losses and TSS, for this study case. Indeed, for the infiltration trench receiving STE with lower pollution levels (2.2 mg TSS. L -1 , 26 mg COD. L -1 ), the infiltration capacity is maintained over the years (4-6 mm h -1 ) and reed roots developed deeper in the soil. A sludge deposit present at the bottom of the second infiltration trench receiving higher pollution levels (7.2 mg TSS. L -1 , 45 mg COD. L -1 , plus episodic sludge release) could lead roots to develop close to the surface affecting the infiltration capacity which did not evolve over time. This work highlights the importance of long-term flow pathway monitoring in understanding the hydraulic behavior of infiltration surfaces submitted to STE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Molecular profile of resected stage I-II non-small cell lung cancer (NSCLC) would help refine prognosis and personalize induction or adjuvant strategies. We sought to report the molecular profile of resected stage I-II NSCLC and analyzed the impact of epidermal growth factor receptor (EGFR) mutations on outcomes in a Western population., Patients and Methods: Surgical cases were identified from Biomarkers France study, a nationwide prospective study including NSCLC patients screened for EGFR, HER2, KRAS, BRAF, PIK3CA, ALK alterations from 2012 to 2013. Among surgical patients, clinical charts of the largest centers were reviewed in order to analyze the prognostic impact of EGFR mutations., Results: In the BMF database (n = 17.636), surgical patients (n = 854) were characterized by a higher proportion of EGFR mutations than nonsurgical patients (12.9% vs. 10.2%, P = .025), while the other molecular alterations did not differ. The proportion of EGFR mutations was 27% in women undergoing surgery. In the study group (n = 293; EGFR wild type, n = 235; usual mutation, n = 50; rare mutation, n = 8), after a median follow-up of 67 months, 215 patients (74.4%) had not relapsed. No difference was found between EGFR-mutant and EGFR-wt tumors regarding recurrence site, disease-free survival, and overall survival. The 5-year disease-free survival and overall survival after surgical resection of stage I-II EGFR-mutated tumors were 65% and 75%, respectively., Conclusion: In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival., Competing Interests: Disclosure Dr Mordant, Dr Brosseau, Dr Milleron, Dr Santelmo, Dr Fraboulet, Mrs Langlais, Dr Gossot, Dr Thomas, Dr Pujol, Dr Madelaine, Dr Lamy, Dr Missy, Dr Blons report no conflict of interest. Dr Besse reports grants from Abbvie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Ignyta, IPSEN, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunotherapeutics, Pfizer, Pharma Mar, Roche-Genentech, Sanofi, Servier, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, Tolero Pharmaceuticals, during the conduct of the study. Dr Ricordel reports grants from Novartis, outside the submitted work. Dr Audigier-Valette reports personal fees and non-financial support from Roche, BMS, MSD, AstraZeneca, Abbvie, Pfizer, Takeda outside the submitted work. Dr Barlesi reports personal fees from Astra-Zeneca, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda, outside the submitted work. Dr Westeel reports honoraria from Roche, AstraZeneca, BMS and MSD and non-financial support from Roche and Pfizer., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

A series of novel 2,9- bis [(substituted-aminomethyl)]-4,7-phenyl-1,10-phenanthroline derivatives was designed, synthesized, and evaluated in vitro against three protozoan parasites ( Plasmodium falciparum , Leishmania donovani and Trypanosoma brucei brucei ). Pharmacological results showed antiprotozoal activity with IC 50 values in the sub and μM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The substituted diphenylphenanthroline 1l was identified as the most potent antimalarial derivative with a ratio of cytotoxic to antiparasitic activities of 505.7 against the P. falciparum CQ-resistant strain W2. Against the promastigote forms of L. donovani , the phenanthrolines 1h , 1j , 1n and 1o were the most active with IC 50 from 2.52 to 4.50 μM. The phenanthroline derivative 1o was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 91 on T. brucei brucei strain. FRET melting and native mass spectrometry experiments evidenced that the nitrogen heterocyclic derivatives bind the telomeric G-quadruplexes of P. falciparum and Trypanosoma . Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma could be considered to be possible targets of this kind of nitrogen heterocyclic derivatives, their potential ability to stabilize the parasitic telomeric G-quadruplexes have been determined through the FRET melting assay and by native mass spectrometry.

Hereditary symbioses have the potential to drive transgenerational effects, yet the mechanisms responsible for transmission of heritable plant symbionts are still poorly understood. The leaf symbiosis between Dioscorea sansibarensis and the bacterium Orrella dioscoreae offers an appealing model system to study how heritable bacteria are transmitted to the next generation. Here, we demonstrate that inoculation of apical buds with a bacterial suspension is sufficient to colonize newly formed leaves and propagules, and to ensure transmission to the next plant generation. Flagellar motility is not required for movement inside the plant but is important for the colonization of new hosts. Further, tissue-specific regulation of putative symbiotic functions highlights the presence of two distinct subpopulations of bacteria in the leaf gland and at the shoot meristem. We propose that bacteria in the leaf gland dedicate resources to symbiotic functions, while dividing bacteria in the shoot tip ensure successful colonization of meristematic tissue, glands, and propagules. Compartmentalization of intrahost populations together with tissue-specific regulation may serve as a robust mechanism for the maintenance of mutualism in leaf symbiosis. IMPORTANCE Hereditary symbioses with bacteria are common in the animal kingdom, but relatively unexplored in plants. Several plant species form associations with bacteria in their leaves, which is called leaf symbiosis. These associations are highly specific, but the mechanisms responsible for symbiont transmission are poorly understood. Using the association between the yam species Dioscorea sansibarensis and Orrella dioscoreae as a model leaf symbiosis, we show that bacteria are distributed to specific leaf structures via association with shoot meristems. Flagellar motility is required for initial infection but does not contribute to spread within host tissue. We also provide evidence that bacterial subpopulations at the meristem or in the symbiotic leaf gland differentially express key symbiotic genes. We argue that this separation of functional symbiont populations, coupled with tight control over bacterial infection and transmission, explain the evolutionary robustness of leaf symbiosis. These findings may provide insights into how plants may recruit and maintain beneficial symbionts at the leaf surface.

Plant epigenetic regulations are involved in transposable element silencing, developmental processes and responses to the environment 1-7 . They often involve modifications of DNA methylation, particularly through the DEMETER (DME) demethylase family and RNA-dependent DNA methylation (RdDM) 8 . Root nodules host rhizobia that can fix atmospheric nitrogen for the plant's benefit in nitrogen-poor soils. The development of indeterminate nodules, as in Medicago truncatula, involves successive waves of gene activation 9-12 , control of which raises interesting questions. Using laser capture microdissection (LCM) coupled to RNA-sequencing (SYMbiMICS data 11 ), we previously identified 4,309 genes (termed NDD) activated in the nodule differentiation and nitrogen fixation zones, 36% of which belong to co-regulated genomic regions dubbed symbiotic islands 13 . We found MtDME to be upregulated in the differentiation zone and required for nodule development, and we identified 474 differentially methylated regions hypomethylated in the nodule by analysing ~2% of the genome 4 . Here, we coupled LCM and whole-genome bisulfite sequencing for a comprehensive view of DNA methylation, integrated with gene expression at the tissue level. Furthermore, using CRISPR-Cas9 mutagenesis of MtDRM2, we showed the importance of RdDM for CHH hypermethylation and nodule development. We thus proposed a model of DNA methylation dynamics during nodule development., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Rhizobium-legume nitrogen-fixing symbiosis involves the formation of a specific organ, the root nodule, which provides bacteria with the proper cellular environment for atmospheric nitrogen fixation. Coordinated differentiation of plant and bacterial cells is an essential step of nodule development, for which few transcriptional regulators have been characterized. Medicago truncatula ETHYLENE RESPONSE FACTOR REQUIRED FOR NODULE DIFFERENTIATION (MtEFD) encodes an APETALA2/ETHYLENE RESPONSIVE FACTOR (ERF) transcription factor, the mutation of which leads to both hypernodulation and severe defects in nodule development. MtEFD positively controls a negative regulator of cytokinin signaling, the RESPONSE REGULATOR 4 (MtRR4) gene. Here we showed that that the Mtefd-1 mutation affects both plant and bacterial endoreduplication in nodules, as well as the expression of hundreds of genes in young and mature nodules, upstream of known regulators of symbiotic differentiation. MtRR4 expressed with the MtEFD promoter complemented Mtefd-1 hypernodulation but not the nodule differentiation phenotype. Unexpectedly, a nonlegume homolog of MtEFD, AtERF003 in Arabidopsis (Arabidopsis thaliana), could efficiently complement both phenotypes of Mtefd-1, in contrast to the MtEFD paralog MtEFD2 expressed in the root and nodule meristematic zone. A domain swap experiment showed that MtEFD2 differs from MtEFD by its C-terminal fraction outside the DNA binding domain. Furthermore, clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9 (CRISPR-Cas9) mutagenesis of MtEFD2 led to a reduction in the number of nodules formed in Mtefd-1, with downregulation of a set of genes, including notably NUCLEAR FACTOR-YA1 (MtNF-YA1) and MtNF-YB16, which are essential for nodule meristem establishment. We, therefore, conclude that nitrogen-fixing symbiosis recruited two proteins originally expressed in roots, MtEFD and MtEFD2, with distinct functions and neofunctionalization processes for each of them., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In this article, we propose to determine the dynamic model of a squirrel-cage induction motor from a reduced amount of information. An adaptive observer is also built from this model in order to obtain a speed estimation and to perform rotor fault monitoring by Tacholess Order Tracking (TOT). We also propose a generalization of the notion of angular sampling in order to adapt to this type of defect. The procedure is validated in the laboratory on a test bench dedicated to the study of rotor bar defects.

Parkinson's disease is a complex neurodegenerative disorder resulting in a multifaceted clinical presentation which includes bradykinesia combined with either rest tremor, rigidity, or both, as well as many non-motor symptoms. The motor features of the disorder are associated with the pathological form of alpha synuclein aggregates and fibrils in Lewy bodies and loss of dopaminergic neurons in the substantia nigra. Parkinson's disease is increasingly considered as a group of underlying disorders with unique genetic, biological, and molecular abnormalities that are likely to respond differentially to a given therapeutic approach. For this reason, it is clinically challenging to treat and at present, no therapy can slow down or arrest the progression of Parkinson's disease. There is a clear unmet clinical need to develop reliable diagnostic and prognostic biomarkers. When disease-modifying treatments become available, prognostic biomarkers are required to support a definitive diagnosis and clinical intervention during the long prodromal period as no clinical implications or symptoms are observed. Robust diagnostic biomarkers would also be useful to monitor treatment response. Potential biomarkers for the sporadic form of Parkinson's disease have mostly included synuclein species (monomer, oligomer, phosphorylated, Lewy Body enriched fraction and isoforms). In this review, we consider the analysis of synuclein and its proteoforms in biological samples using proteomics techniques (immunoassay and mass spectrometry) applied to neurodegenerative disease research., Competing Interests: M-LP, NL, and SM were employed by the company Shimadzu Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pons, Loftus, Vialaret, Moreau, Lehmann and Hirtz.)

Purpose: Thiel's body preservation method allows the donor body to retain color and soft tissue that are similar to those of a living individual. Since its initial description, the technique has not been developed much. Here, we propose a simpler protocol applied to the head and neck, making the technique easier, cheaper, and more accessible to a greater number of medical schools., Methods: The modified Thiel technique was applied to three heads separated from the body, followed by 6 h of perfusion and 6 weeks of fixation. This technique was compared with formalin (three heads) and freeze (three heads) preservations during academic training in head and neck surgery. Anatomical dissections included a parotid gland dissection, a submandibular gland dissection, an otologic and an endonasal dissection. Twelve surgeons blindly assessed the three types of preservations using a standardized questionnaire., Results: The modified Thiel technique made possible better quality of dissection and tissue identification, with the exception of endonasal dissection. Concerning the endonasal dissection, the modified Thiel technique ranked best for smell, but all other criteria ranked lower than the freezing method. For the submandibular and parotid gland dissections, the modified Thiel technique was ranked best, with statistically significant differences (p < 0.002) for all items. The modified Thiel technique also ranked significantly better during otologic surgery regarding the quality of the skin/eardrum, bone, and muscle, and the smell., Conclusion: This study demonstrated that the modified Thiel technique is an embalming technique which improves the quality of head and neck surgical anatomy education., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Current multiagent chemotherapy regimens have improved the cure rate in acute leukemia patients, but they are highly toxic and poorly efficient in relapsed patients. To improve the treatment approaches, new specific molecules are needed. The G-quadruplexes (G4s), which are noncanonical nucleic acid structures found in specific guanine-rich DNA or RNA, are involved in many cellular events, including control of gene expression. G4s are considered as targets for the development of anticancer agents. Heterocyclic molecules are well known to target and stabilize G4 structures. Thus, a new series of 2,9-bis[(substituted-aminomethyl)phenyl]-1,10-phenanthroline derivatives (1a-i) was designed, synthesized, and evaluated against five human myeloid leukemia cell lines (K562, KU812, MV4-11, HL60, and U937). Their ability to stabilize various oncogene promoter G4 structures (c-MYC, BCL-2, and K-RAS) as well as the telomeric G4 was also determined through the fluorescence resonance energy transfer melting assay and native mass spectrometry. In addition, the more bioactive ligands 1g-i were tested for telomerase activity in HuT78 and MV4-11 protein extracts., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Draf III frontal sinusotomy is one of the most complex surgical procedures on the frontal sinus, designed to limit the risks of restenosis by ensuring unification of the two ostia and resection of the floor of the sinus. This procedure requires a good knowledge of anatomy and sufficient surgical expertise to avoid the risk of CSF leak and to limit the risk of restenosis. The surgeon can use various landmarks, consisting of foramina, bone grooves and arteries located on the anterior part of the cribriform plate to guide the procedure. The purpose of this technical note is to explain the use of these landmarks to ensure safe Draf III frontal sinusotomy via a medial approach., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The current decline of wild bees puts important ecosystem services such as pollination at risk. Both inventory and monitoring programs are needed to understand the causes of wild bee decline. Effective insect monitoring relies on both mass-trapping methods coupled with rapid and accurate identifications. Identifying wild bees using only morphology can be challenging, in particular, specimens from mass-trapped samples which are often in poor condition. We generated DNA barcodes for 2931 specimens representing 157 species (156 named and one unnamed species) and 28 genera. Automated cluster delineation reveals 172 BINs (Barcodes Index Numbers). A total of 36 species (22.93%) were found in highly urbanized areas. The majority of specimens, representing 96.17% of the species barcoded form reciprocally exclusive groups, allowing their unambiguous identification. This includes several closely related species notoriously difficult to identify. A total of 137 species (87.26%) show a "one-to-one" match between a named species and the BIN assignment. Fourteen species (8.92%) show deep conspecific lineages with no apparent morphological differentiation. Only two species pairs shared the same BIN making their identification with DNA barcodes alone uncertain. Therefore, our DNA barcoding reference library allows reliable identification by non-experts for the vast majority of wild bee species in the Loire Valley.

Endogenous viruses form an important proportion of eukaryote genomes and a source of novel functions. How large DNA viruses integrated into a genome evolve when they confer a benefit to their host, however, remains unknown. Bracoviruses are essential for the parasitism success of parasitoid wasps, into whose genomes they integrated ~103 million years ago. Here we show, from the assembly of a parasitoid wasp genome at a chromosomal scale, that bracovirus genes colonized all ten chromosomes of Cotesia congregata. Most form clusters of genes involved in particle production or parasitism success. Genomic comparison with another wasp, Microplitis demolitor, revealed that these clusters were already established ~53 mya and thus belong to remarkably stable genomic structures, the architectures of which are evolutionary constrained. Transcriptomic analyses highlight temporal synchronization of viral gene expression without resulting in immune gene induction, suggesting that no conflicts remain between ancient symbiotic partners when benefits to them converge.

Bio-based aerogels containing cellulose nanofibrils (CNFs) are promising materials due to the inherent physical properties of CNF. The high affinity of cellulose to plant hemicelluloses (xyloglucan, xylan, pectin) is also an opportunity to develop biomaterials with new properties. Here, we prepared aerogels from gelled dispersions of CNFs and xyloglucan (XG) at different ratios by using a freeze-casting procedure in unidirectional (UD) and non-directional (ND) manners. As showed by rheology analysis, CNF and CNF/XG dispersions behave as true gels. We investigated the impact of the freezing procedure and the gel's composition on the microstructure and the water absorption properties. The introduction of XG greatly affects the microstructure of the aerogel from lamellar to cellular morphology. Bio-based aerogels showed high water absorption capacity with shape recovery after compression. The relation between morphology and aerogel compositions is discussed.

Objectives: Tumor mutation screening is standard of care for patients with stage IV NSCLC. Since a couple of years, widespread NGS approaches used in routine diagnostics to detect driver mutations such as EGFR, KRAS, BRAF or MET allows the identification of other alterations that could modulated the intensity or duration of response to targeted therapies. The prevalence of co-occurring alterations that could affect response or prognosis as not been largely analyzed in clinical settings and large cohorts of patients. Thanks to the IFCT program "Biomarkers France", a collection of samples and data at a nation-wide level was available to test the impact of co-mutations on first line EGFR TKI in patients with EGFR mutated cancers., Materials and Methods: Targeted NGS was assessed on available (n = 208) samples using the Ion AmpliSeq™ Cancer Hotspot Panel v2 to screen for mutations in 50 different cancer genes., Results: This study showed that PTEN inactivating mutations, ATM alterations, IDH1 mutations and complex EGFR mutations were predictors of short PFS in patients with a stage 4 lung adenocarcinoma receiving first line EGFR TKI and that PTEN, ATM, IDH1 and KRAS mutations as well as alterations in the MAPK pathway were related to shorter OS., Conclusion: These findings may lead to new treatment options in patients with unfavorable genotypes to optimize first line responses., (Copyright © 2020. Published by Elsevier B.V.)

The stimulation of plant innate immunity by elicitors is an emerging technique in agriculture that contributes more and more to residue-free crop protection. Here, we used RNA-sequencing to study gene transcription in tomato leaves treated three times with the chitooligosaccharides-oligogalacturonides (COS-OGA) elicitor FytoSave ® that induces plants to fend off against biotrophic pathogens. Results showed a clear upregulation of sequences that code for chloroplast proteins of the electron transport chain, especially Photosystem I (PSI) and ferredoxin. Concomitantly, stomatal conductance decreased by half, reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] content and reactive oxygen species production doubled, but fresh and dry weights were unaffected. Chlorophyll, β-carotene, violaxanthin, and neoxanthin contents decreased consistently upon repeated elicitations. Fluorescence measurements indicated a transient decrease of the effective PSII quantum yield and a non-photochemical quenching increase but only after the first spraying. Taken together, this suggests that plant defense induction by COS-OGA induces a long-term acclimation mechanism and increases the role of the electron transport chain of the chloroplast to supply electrons needed to mount defenses targeted to the apoplast without compromising biomass accumulation., Competing Interests: GVA and PVC are members of FytoFend S.A. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Moreau, van Aubel, Janky and Van Cutsem.)

A series of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline, and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives was designed, synthesised, and evaluated in vitro against three protozoan parasites ( Plasmodium falciparum , Leishmania donovani , and Trypanosoma brucei brucei ). Biological results showed antiprotozoal activity with IC 50 values in the µM range. In addition, the in vitro cytotoxicity of these original molecules was assessed with human HepG2 cells. The quinoline 1c was identified as the most potent antimalarial candidate with a ratio of cytotoxic to antiparasitic activities of 97 against the P. falciparum CQ-sensitive strain 3D7. The quinazoline 3h was also identified as the most potent trypanosomal candidate with a selectivity index (SI) of 43 on T. brucei brucei strain. Moreover, as the telomeres of the parasites P. falciparum and Trypanosoma are possible targets of this kind of nitrogen heterocyclic compounds, we have also investigated stabilisation of the Plasmodium and Trypanosoma telomeric G-quadruplexes by our best compounds through FRET melting assays.

Contactless broadband microwave spectroscopy (a.k.a., broadband dielectric spectroscopy (BDS)) enables the accurate operando analysis of the electrical and magnetic properties without compromising the kinetic conditions of the experiment. The BDS method is sensitive to the actual electronic structure of species, and it is most relevant to redox reactions involving charge-transfer. In this paper, using BDS, we have studied and characterized the oxidation of a copper layer in a purposely built prototypical 3-D integrated circuit (3D-IC) during cycled high-temperature storage. We show that the microwave signal loss in these devices is attributable to the energy dissipation through the signal's interactions with the copper oxidation product. The results demonstrate that contactless BDS could be leveraged into an excellent metrology for applications that use metal oxide as sensing elements.

Objectives: The aim of this study was to evaluate peri- and post-operative complications related to cochlear implantations. We searched for risk factors predicting these complications and analyzed the complications in the youngest and most elderly., Study Design: Retrospective analysis of cochlear implant patients., Materials and Methods: All patients who underwent cochlear implantation in France between January 2012 and December 2016 were anonymized and registered in the EPIIC database. This population included 3483 adults and 2245 children. Their demographic and surgical data and their incidence of peri- or post-operative complications, including their severity, whether major or minor, were all indicated., Results: The global complication rate was 6.84%. The risk of complication was higher in initial implantation versus reimplantation (P<0.0001). The risk was also higher for bilateral implantation versus unilateral (P<0.0001). Complications were more frequent for patients with cochlear malformation (P=0.002). There was no difference in complication rates across age groups; babies under 1 year old, and the elderly over 80 and even over 90, did not have more complications than the rest of the population. Patients treated in the daily care unit had no more complications than those who were hospitalized for one night or more (P=0.64)., Conclusion: Cochlear implantation is a safe technique with a low incidence of complications. The absence of increased risk in patients at the extremes of the age spectrum justifies offering this solution to all, without age limitation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This study aims to determine the frequency and causes of cochlear explants with re-implantation (ERI) after 5 years' follow up of the patients included in the French national EPIIC (étude post-inscription des implants cochléaires) registry tracking patients with cochlear implantation. This multicenter, descriptive prospective study was conducted on 5051 patients enrolled in the EPIIC database between January 2012 and December 2016. Ninety-five patients (1.9%) received a primary implant and an ERI during the study. Of these, four benefitted from two ERIs. The number of ERIs was significantly higher in the pediatric population than among adults. The explantation and reimplantation were performed simultaneously in 86% of cases. The reasons for explantation were: in 46.4% of cases linked to a malfunction of the implant, and in 39.3% of cases for medical or surgical reasons. The number of electrodes inserted was significantly higher after the ERI than after the first implantation. There was just one post-ERI infection for these 95 explanted and re-implanted patients. As well as explantation with reimplantation rarely being necessary, it generally presents no major surgical difficulty and in most cases it allows a better integration than in the first implantation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: Evaluate in France the outcomes of cochlear implantation outside the selection criteria, off-label., Material and Methods: This is a prospective cohort study including adults and children having received a cochlear implant (CI) in an off-label indication, that is outside the criteria established by the "Haute Autorité de santé (HAS)" in 2012. The data was collected from the "EPIIC" registry on recipients who received CIs in France between 2011 and 2014. Speech audiometry was performed at 60dB preimplantation and after one year of CI use, as well as an evaluation of the scores of the quality of life with the APHAB questionnaire, the scores for CAP and the professional/academic status in pre- and post-implantation conditions. Major and minor complications at surgery have been recorded., Results: In total, 590 patients (447 adults and 143 children) with an off-label indication for CIs were included in this study from the EPIIC registry (11.7% of the whole cohort of EPIIC). For adults, the median percentage of comprehension using monosyllabic word lists was 41% in preimplantation condition versus 53% after one year of CI use (P<0.001) and 60% versus 71% in dissyllabic word lists (P<0.001). The CAP scores were 5 versus 6 in pre- and post-implantation conditions respectively (P<0.001) and the APHAB scores were statistically lower after implantation (P<0.001). In the children cohort, the median percentage of comprehension using monosyllabic word lists was 51% in preimplantation condition and 65% after CI (P<0.001), and 48% versus 82% (P<0.001) for dissyllabic word lists. The CAP scores were 5 versus 7 respectively in pre- and post-CI conditions (P<0.001). Thirty-two minor complications (5.4%) and 17 major complications (2.8%) were reported in our panel of off-label indication patients., Conclusion: These results suggest that a revision of the cochlear implantation candidacy criteria is necessary to allow more patients with severe or asymmetric hearing loss to benefit from a CI when there is an impact on quality of life despite the use of an optimal hearing aid., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

This study concerns the results of cochlear implantation in children and adults from French cochlear implantation centers, monitored at one, two and three years by the Cochlear Implant French Registry EPIIC. This multicenter study enrolled 2603 subjects (1667 adults and 936 children) implanted in one ear. The following parameters were studied: hearing overall performances, monosyllabic or dissyllabic word perception, speech intelligibility, self-assessment questionnaire of Cochlear Implant (CI) benefits (Abbreviated profile of Hearing aid Benefit); professional activity and schooling. This study confirms the ceiling effect in adults' performances after the 1 st year and the progressive growth in children's performances. It also shows that the contralateral hearing aid enhances performances compared to the CI alone condition, in all follow-up sessions. The French register of CIs is the only worldwide register of systematic follow-up on a period of three years and more of all adults and children implanted in a country., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objective: Multi-centre study of the National French Registry (EPIIC) of patients with cochlear implants, focusing on infants who were operated-on under the age of 24 months between 2012 and 2016., Patients and Methods: A total of 615 profoundly deaf infants, who received cochlear implants (CIs) before their second birthday, were included in the registry by different CI centers. Epidemiological, surgical, speech therapy and school, follow-up data were included in the registry, 12, 24, 36 and 48 months thereafter. The following parameters were studied: type of implantation (uni- or bilateral), complications, cause of deafness, category of auditory perception (CAP), Open-set word recognition score (OSW), speech intelligibility rating, lexical comprehension with EVIP (Peabody), communication mode and type of schooling. Bilateral simultaneous CI (BiCI) and unilateral CI (UniCI) groups were compared., Results: There were 744 implantations. The explantation-reimplantation rate, within the four-year follow-up, was just 3.6%. Mean implantation age was 16.0 months, and similar in the two groups (BiCI/UniCI). A total of 51% of children had their first implant between 12 and 18 months, and 15% before 12 months. Implantation was unilateral in 52% of cases. Fifty-six percent of the bilateral procedures were sequential, with a mean delay of 16.8 months for the second implantation. The cause of deafness was unknown in 52% of cases. Of the 48% (297/615) of attributed cases, 32% had clear genetic causes. The remaining deafness was due to cytomegalovirus (CMV, 8%), inner-ear malformation (5%) and meningitis (3%). The main complications were from infections (47%) and internal device failure (25%). Four years post-operation, 84% of the UniCI and 75% of BiCl groups had a CAP≥5, and 83% of UniCl and 100% BiCI had OSW≥80%. Furthermore 74% of UniCI and 77% of BiCI communicated orally and 85% of UniCI and 90% of BiCI integrated into mainstream schooling., Conclusion: The French Registry of cochlear implants (EPIIC) is the only such national registry in the world. Our analysis illustrates the immediate benefits of, either single or double, cochlear implantation for language, perception skills and schooling., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: To analyze the performance of cochlear implants in French patients aged 65 and over, implanted between 2012 and 2016, using data from the French national registry for cochlear implants (EPIIC)., Materials and Methods: The French national registry incorporates patient data from before implantation and for three years after implantation, stratified in different age groups (18-39, 40-64years, 65-74years and>75years). Here, we assessed the latter two categories. Hearing was assessed using mono- and disyllabic words in a silent background. The Category of Auditory Performance (CAP) scale was also implemented and subjects took the Abbreviated Profile of Hearing Aid Benefit (Aphab) questionnaire., Results: The population aged over 65 accounted for 38% (n=1193) of the 3178 adult implanted patients. The performance for mono- and disyllabic words in silence, the CAP scores and the APHAB questionnaire answers for ease of communication, background noise and reverberation were dramatically improved at one year post-implantation (P<0.0001 for each score) and remained stable between one and three years thereafter. The percentage improvement was similar across all age groups. The scores for loud-noise intolerance did not change after cochlear implantation in any age group., Conclusion: Cochlear implants improve hearing and communication in subjects aged 65 and over, with comparable efficiency to that achieved in younger subjects. Cochlear implantation should thus be proposed whenever hearing aids provide only limited benefit. However, between 2012 and 2016, cochlear implantation was given to less than 1% of the French population aged 65 and over with profound deafness., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: Assessment of the incidence and results of bilateral cochlear implantation in adults and children in France., Materials and Methods: Multicenter retrospective study of data in the French national registry of cochlear implantations from January 1st 2012 to December 31st 2016. Functional results from CAP (Category of Auditory Performance) questionnaires and speech audiometry tests, with mono- and di-syllabic word-lists, were compared before and after implantation. Speech audiometry tests were carried out against a noisy background, except before simultaneous implantations., Results: Nine hundred and forty two bilateral cochlear implantations were performed during this period, that is, 16.4% of all cochlear implantations. Five hundred and eighty eight bilateral implantations were performed sequentially. 59% of the bilateral implantations were performed in children. Bilateral implants significantly improved CAP scores in all cases (P<0.001). Auditory performance, with the two types of word-list, were significantly improved after simultaneous implantation (P<0.01). After sequential implantation, the speech discrimination score, already very good with the first implant, reached 63±26% [0-100] with monosyllabic word lists, and 72±28% [0-100] with dissyllabic words. There were more complications due to surgery in bilateral cases than in the entire population of cochlear recipients (9.1% vs 6.4%, P<0.02)., Conclusion: Hearing is significantly improved by simultaneous cochlear implantation. For sequential implantation, at one year, when auditory results were already excellent from the first implant, in the bimodal condition CAP scores were significantly improved, although there was no further change in speech audiometry in noise., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Cochlear and brainstem implants have been included on the list of reimbursable products (LPPR) in France since March of 2009. The implants were initially inscribed for 5 years, after which an application for renewal with the French National Commission for the Evaluation of Medical Devices and Health Technologies (Commission Nationale d'évaluation des dispositifs médicaux et des technologies de santé - CNEDiMTS) was required [Haute Autorité de santé, 2009]. Upon registration to the list of reimbursable products, the companies and the reference centers for cochlear and brainstem implants were asked to set up a post-registration registry called EPIIC. This article reports the evolution in the EPIIC registry of the general indicators for 5051 patients over the five years from 2012-2016., (Copyright © 2020. Published by Elsevier Masson SAS.)

In the Southern Ocean, large-scale phytoplankton blooms occur in open water and the sea-ice zone (SIZ). These blooms have a range of fates including physical advection, downward carbon export, or grazing. Here, we determine the magnitude, timing and spatial trends of the biogeochemical (export) and ecological (foodwebs) fates of phytoplankton, based on seven BGC-Argo floats spanning three years across the SIZ. We calculate loss terms using the production of chlorophyll-based on nitrate depletion-compared with measured chlorophyll. Export losses are estimated using conspicuous chlorophyll pulses at depth. By subtracting export losses, we calculate grazing-mediated losses. Herbivory accounts for ~90% of the annually-averaged losses (169 mg C m -2 d -1 ), and phytodetritus POC export comprises ~10%. Furthermore, export and grazing losses each exhibit distinctive seasonality captured by all floats spanning 60°S to 69°S. These similar trends reveal widespread patterns in phytoplankton fate throughout the Southern Ocean SIZ.

Background: Despite the development of anterior skull base surgery, the anatomy of the nasal bone and anterior cribriform plate remains unclear. A recent study confirmed 2 distinct foramina in the anterior part of cribriform plate: the ethmoidal slit (ES) and the cribroethmoidal foramen (CF). The aim of this study was to specify their content, their anatomic relationship to the frontal sinus and skull base, and their potential value in skull base surgery., Methods: Dissections were performed on 36 cadaver heads. Macro- and microscopic examinations were carried out. Microcomputed tomography scans contrasted with osmium were performed to identify vessels and nerves. Histology with neural, meningeal, or luteinizing hormone-releasing hormone immunomarkers was performed on the content of the foramina. Finally, endonasal surgical dissections were carried out., Results: The ES and the CF were observed in all cases. They measured a mean of 4.2 and 1.6 mm, respectively. The ES contained dura mater, arachnoid tissues, lymphatics, and the terminal nerve. The CF contained the anterior ethmoidal nerve and artery. This foramen continued forward with the cribroethmoidal groove, which measured a mean of 2.5 mm. This groove was under the frontal sinus and in front of the skull base. We also described a "cribroethmoidal canal" and a "nasal bone foramen.", Conclusion: The clinical applications of this new anatomic description concern both cribriform plate and frontal sinus surgeries. Identifying the terminal nerve passing through the ES is a step forward in understanding pheromone recognition in humans., (© 2019 ARS-AAOA, LLC.)

Two series of piperazinyl-pyrrolo[1,2- a ]quinoxaline derivatives were prepared via a Buchwald-Hartwig cross-coupling reaction and then evaluated for their ability to inhibit the drug efflux activity of CaCdr1p and CaMdr1p transporters of Candida albicans overexpressed in a Saccharomyces cerevisiae strain. In the initial screening of twenty-nine piperazinyl-pyrrolo[1,2- a ]quinoxaline derivatives, twenty-three compounds behaved as dual inhibitors of CaCdr1p and CaMdr1p. Only four compounds showed exclusive inhibition of CaCdr1p or CaMdr1p. Further biological investigations were developed and for example, their antifungal potential was evaluated by measuring the growth of control yeast cells (AD1-8u - ) and efflux pump-overexpressing cells (AD-CDR1 and AD-MDR1) after exposition to variable concentrations of the tested compounds. The MIC 80 values of nineteen compounds ranging from 100 to 901 μM for AD-CDR1 demonstrated that relative resistance index (RI) values were between 8 and 274. In comparison, only seven compounds had RI values superior to 4 in cells overexpressing Mdr1p. These results indicated substrate behavior for nineteen compounds for CaCdr1p and seven compounds for CaMdr1p, as these compounds were transported via MDR transporter overexpressing cells and not by the AD1-8u - cells. Finally, in a combination assay with fluconazole, two compounds (1d and 1f) have shown a synergistic effect (fractional inhibitory concentration index (FICI) values ≤ 0.5) at micromolar concentrations in the AD-MDR1 yeast strain overexpressing CaMdr1p-protein, indicating an excellent potency toward chemosensitization., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: In people with chronic low back pain (cLBP) and active discopathy, glucocorticoid intradiscal injection (GC IDI) reduces LBP in the short-term. Lumbosacral immobilization may be useful to obtain long-term results., Objective: To assess the feasibility of a lumbosacral immobilization using a pantaloon cast following GC IDI in people with cLBP sand active discopathy., Methods: We conducted a retrospective feasibility study. Participants were allocated to experimental or control groups by preferences. The experimental group received lumbosacral immobilization using a custom-made pantaloon cast worn continuously for one week following a GC IDI of 25 mg of prednisolone acetate. The control group received GC IDI alone. The primary endpoint was the feasibility of lumbosacral immobilization assessed by the rate of refusal and early withdrawal of the cast., Results: Twelve patients were offered lumbosacral immobilization following GC IDI: the rate of refusal was 3/12 (25.0%) and was 3/9 (33.3%) of early withdrawal. Mean (95% CI) acceptability of the procedure was 55.0 (26.9-83.1)/100 in the experimental group (N= 6) and 61.6 (25.1-98.2)/100 in the control group (N= 6)., Conclusions: We found high rates of refusal and early withdrawal of the lumbosacral immobilization using a pantaloon cast following GC IDI in people with nonspecific cLBP and active discopathy.