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A population of 96 doubled haploid lines (DHLs) was prepared from F 1 plants of the hexaploid wheat cross Chinese Spring × SQ1 (a high abscisic acid-expressing breeding line) and was mapped with 567 RFLP, AFLP, SSR, morphological and biochemical markers covering all 21 chromosomes, with a total map length of 3,522 cM. Although the map lengths for each genome were very similar, the D  genome had only half the markers of the other two genomes. The map was used to identify quantitative trait loci (QTLs) for yield and yield components from a combination of 24 site × treatment × year combinations, including nutrient stress, drought stress and salt stress treatments. Although yield QTLs were widely distributed around the genome, 17 clusters of yield QTLs from five or more trials were identified: two on group 1 chromosomes, one each on group 2 and group 3, five on group 4, four on group 5, one on group 6 and three on group 7. The strongest yield QTL effects were on chromosomes 7AL and 7BL, due mainly to variation in grain numbers per ear. Three of the yield QTL clusters were largely site-specific, while four clusters were largely associated with one or other of the stress treatments. Three of the yield QTL clusters were coincident with the dwarfing gene Rht-B1 on 4BS and with the vernalisation genes Vrn-A1 on 5AL and Vrn-D1 on 5DL. Yields of each DHL were calculated for trial mean yields of 6 g plant −1 and 2 g plant −1 (equivalent to about 8 t ha −1 and 2.5 t ha −1, respectively), representing optimum and moderately stressed conditions. Analyses of these yield estimates using interval mapping confirmed the group-7 effects on yield and, at 2 g plant −1, identified two additional major yield QTLs on chromosomes 1D and 5A. Many of the yield QTL clusters corresponded with QTLs already reported in wheat and, on the basis of comparative genetics, also in rice. The implications of these results for improving wheat yield stability are discussed. [ABSTRACT FROM AUTHOR]

A reproducible method for sequential study of migration out of human skin, phagocytosis and bactericidal activity of neutrophils is described. Untreated psoriatics exhibit an early increase of chemotactic activity (0-8 hr, p < 0.02) and subsequently a strong inhibition of chemotaxis (8-24 hr, p < 0.01), a slight decrease of phagocytosis and a decrease in bactericidal activity (20 min, p < 0.02; 30 min, p < 0.003); 60 min, p < 0.001; 120 min, p < 0.001) as compared with controls. After clearing of skin lesions, the early increased chemotactic activity returned to normal values but the subsequent chemotactic inhibition remains as strong as before treatment. Phagocytosis increased to normal values (p < 0.02) and bactericidal activity also increased but remained significantly low. These abnormalities were more evident in migrating than in circulating neutrophils, underlining the sensitivity of the described method. [ABSTRACT FROM AUTHOR]

A new method for studying epidermalization in vitro is described. It consists of inserting a punch biopsy that serves as a source of epidermis into dermal equivalent freshly made up, with fibroblasts mixed in a collagen matrix. Fibroblasts cling to collagen fibrils and contract the matrix, leading in 3 days to a resistant dermal equivalent holding the punch biopsy firmly in place. At day 5, a culture medium favouring epidermal growth was used and a fringe of a new epidermis appeared around the punch, the area of which grew linearly with time. This new epidermis showed a pattern of differentiation similar to epidermis in vivo, with cuboidal basal cells, keratohyalin granules, membrane coating granules and the expression of the 65–67 kd keratin subset. The method seems to combine the advantages of the explant technique and of classical keratinocyte cultures, providing the researcher with a large quantity of differentiated epidermis, the pharmacologist with simple and quantitative system in which to study modifications of growth and differentiation of epidermis, and the plastic surgeon with a possible material for skin grafting. [ABSTRACT FROM AUTHOR]

By using a very sensitive and reproducible skin chamber technique we have shown that the aromatic retinoid etretinate (Ro 10–9359) and its main metabolite (Ro 10–1670) significantly inhibit the migration of neutrophils from the blood to tissues when applied into skin chambers (0·1 mg/ml) or when given orally (1 mg/kg/day for 8 days) to normal volunteers. This pharmacological property could be closely linked to the antipsoriatic properties of these drugs. [ABSTRACT FROM AUTHOR]

Wound healing is a very complex phenomenon involving blood, dermal and epidermal factors. These factors are tightly associated since, for example, dermo-epidermal injuries do cicatrize at a lower rate than same sized pure epidermal wounds (Pollack, 1979). On the other hand, in vivo studies of skin cicatrization are of critical interest since numerous pathological, pharmacological or physical conditions, such as occlusion by polyethylene film (Eaglstein & Mertz, 1978), do modify wound healing. In order to undertake in vivo studies in man for normal or pathological skin cicatrization with or without therapeutic agents, one has to use experimental procedures which fit at least three often conflicting conditions. Firstly, these procedures have to be related to the entire complex phenomenon. Secondly, the methods should give quantitative and reproducible data and, if possible, a kinetic evaluation. Thirdly, experimental procedures have to be as non-invasive as possible in order to be acceptable by human volunteers. Histological procedures have been already performed after dermo-epidermal injuries (Winter, 1972). They gave important qualitative results with regard to the entire phenomenon. However, they are invasive and therefore have been essentially performed on animals. Moreover, as far as histological procedures are concerned, quantitative evaluation is difficult. Therefore more analytical and quantitative experimental procedures are of interest. Using suction blisters, which create pure and reproducible epidermal wounds and leave the basal lamina intact (Ortonne, 1980; Dubertret, Lebreton & Touraine, 1982a, b), one may look more selectively at the epidermal events of skin cicatrization. Such experiments may be qualitative if histological procedures are used and quantitative if planimetric evaluations are performed after dermo-epidermal separation (Eaglstein & Mertz, 1978; Fourtanier et al.-, 1984). However, both procedures are invasive. The aim of our work was to develop a reproducible and non-invasive method allowing quantitative analysis of human epidermal healing. The method we propose is based on the repair of the epidermal barrier function after purely epidermal woimds (Saiag et al., in preparation). [ABSTRACT FROM AUTHOR]

A new host material for Single-Layer Phosphorescent Organic Light-Emitting Diodes (SL-PhOLED) is reported, namely SPA-2-FDMB, using the dimesitylborane (DMB) fragment as an acceptor unit. The molecular design is constructed on the general donor-spiro-acceptor architecture, which consists of connecting, via a spiro bridge, a donor and an acceptor units in order to avoid strong interaction between them. The DMB fragment is known for many electronic applications (notably Aggregation-Induced Emission) but has not been used yet for SL-PhOLED applications. This appears particularly interesting, as the development of this simplified technology has shown that only a few electron-accepting fragments such as diphenylphosphine oxide can provide high-performance devices. Herein, the yellow-emitting SL-PhOLED using SPA-2-FDMB as host presents an External Quantum Efficiency of 8.1% (Current Efficiency of 24.9 cd.A -1 ) with a low threshold voltage of 2.6 V. As SPA-2-FDMB presents a sharp HOMO/LUMO difference, the good matching of HOMO and LUMO energy levels with the Fermi level of the electrodes is responsible for these performances. The low LUMO level of -2.61 eV also appears particularly important. These performances are, to date, the highest reported for a yellow/orange-emitting SL-PhOLED and show the potential of DMB unit in the single-layer technology., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background: Low-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells., Objective: This translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN., Study Design: The expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab., Results: We confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab., Conclusions: Our work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The way that pain is assessed in the PACU could impact on postoperative pain and analgesic consumption. However, there is currently no evidence to support this speculation. The authors hypothesised that using a comfort scale reduces postoperative opioid consumption when compared with a standard numerical rating scale (NRS) to evaluate pain in the PACU., Methods: In this cluster-randomised trial, patients were assessed using either a comfort scale (comfort group) or a pain NRS (NRS group). The primary outcome was the opioid consumption in the PACU. The main secondary outcomes were postoperative pain, nausea and vomiting, length of stay in the PACU, and satisfaction., Results: Of 885 randomised patients, 860 were included in the analysis. Opioid consumption in the PACU was comparable in the comfort and NRS groups (median [interquartile range [IQR] 0 (0-5) vs 0 (0-6); P=0.2436), irrespective of the type of surgical procedure. The majority of patients did not need any postoperative opioid (59% in the comfort group and 56% in the NRS group, P=0.2260). There was no difference in postoperative pain, nausea and vomiting, time to reach an Aldrete score ≥9 after extubation, and global satisfaction., Conclusions: Using a comfort scale to assess pain in the PACU did not spare any opioid compared with use of a standard NRS. Further studies focusing on patients at risk of increased postoperative opioid consumption are necessary., Clinical Trial Registration: NCT05234216., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

In this study, we evaluated the performance of the EUCAST RAST method on a collection of 154 clinical strains of P. aeruginosa, including strains resistant to ceftazidime and carbapenems. While the test is convenient for routine laboratories, we observed significant rates of VME (ranging from 0.0 to 15.0%) and ME (ranging from 1.3 to 16.3%) after 6 h, particularly for key antibiotics such as ceftazidime, piperacillin/tazobactam, and meropenem. Extending the incubation time to 8 h may improve results (CA ranging from 87.2 to 99%), but caution is required in interpretation due to persistence of VME (ranging from 0.0 to 15.6%) and ME (ranging from 0.0 to 11.7%)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The aim of this study was to investigate the association of co-medication with metformin, a statin, or beta blocker with survival in patients with primary ovarian cancer., Methods: Individual data from three phase III, randomized controlled trials (AGO-OVAR 11, AGO-OVAR 12, and AGO-OVAR 16) and one phase II trial (AGO-OVAR 15) were pooled and analyzed. Patients were classified as ever user if the specific co-medication was documented at least once during the trial, and were compared with never users as controls. Association of co-medications and outcomes were adjusted for potential confounders (age, International Federation of Gynecology and Obstetrics stage, histology, residual disease after surgery, Eastern Cooperative Oncology Group (ECOG) performance status, body mass index, Charlson Comorbidity Index, and assigned treatment within the trial) in multivariate Cox regression analyses., Results: Overall, n=2857 patients were included. Ever users were: 100 patients received metformin (3.5%), 226 patients received statins (7.9%), and 475 (16.6%) patients received beta blockers (n=391 selective beta blockers; 84 non-selective beta blockers) as co-medication. There were no significant differences regarding the baseline characteristics except that ever users were significantly older, more obese, and had more comorbidities, according to the Charlson Comorbidity Index, compared with controls. Multivariate analyses for progression free survival and overall survival revealed neither a significant impact of metformin on survival (progression free survival hazard ratio (HR) 0.94, 95% confidence interval CI 0.69 to 1.29, p=0.7; overall survival HR 0.82, 95% CI 0.58 to 1.17, p=0.28) nor for statins (progression free survival HR 0.98, 95% CI 0.82 to 1.18, p=0.87; overall survival HR 0.91, 95% CI 0.74 to 1.12, p=0.37). In contrast, ever users of selective beta blockers had a significantly higher risk for recurrence and death (progression free survival HR 1.22, 95% CI 1.05 to 1.41, p=0.009; overall survival HR 1.25 95% CI 1.06 to 1.47, p=0.009)., Conclusions: In this analysis, co-medication with metformin or statins had no significant impact on survival in patients with primary ovarian cancer. In contrast, co-medication with a beta blocker was associated with worse survival. However, whether this observation is related to the underlying condition rather than a direct negative impact on tumor biology remains unclear., Competing Interests: Competing interests: DD: honoraria: AstraZeneca, GSK, Intuitive, KLS Martin, Merck Sharp & Dohme (MSD); travel/accommodation/expenses: AstraZeneca; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Eisai, GSK, KLS Martin, MSD, PharmaMar, Seagen. FH: personal fees and non-financial support: AstraZeneca, Roche, Tesaro, GSK, Clovis; personal fees: Zailabs and PharmaMar, outside the submitted work. JF: honoraria: Medupdate, Decision Resources, Simon-Kucher and Partners, Juniper, Bionest Partner, Vox Bio, Axiam Healthcare Strategies, Prosapient, Lilly, MedPartners; research funding: Roche Pharma AG, GSK/Tesaro; travel/accommodation/expenses: Roche Pharma AG. PH: grants, personal fees and non-financial support: Astra Zeneca, GSK; grants and personal fees: Roche, MSD, Clovis, Immunogen; personal fees: Sotio, Stryker, Zai Lab, Mersana, Miltenyi; grants: Boehringer lngelheim, Medac, Genmab, Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft, outside the submitted work. PW: Advisory Board Member and received honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche Pharma, Eisai, Clovis, GSK, Daiichi Sankyo. MRM: honoraria: Astra Zeneca, Eisai, Genmab, GSK, Mersana, Takeda, Zailab; travel/accommodation/expenses: AstraZeneca, GSK, Takeda; Advisory Board: Allarity Therapeutics, Astra Zeneca, Biontech, Daiichi-Sankyo, Eisai, Genmab, GSK, lmmunogen, Incyte, Merck/MSD, Mersana, Regeneron, Zailab; Chairman (2020-2022) of the European Network of Gynaecological Oncology Trials group; Vice-President of the European Society of Gynaecological Oncology; Faculty member of the European Society of Medical Oncology; Scientific Chair of the International Gynecologic Cancer Society; stock options: Karyopharm Therapeutics, Sera Prognostics. IRC: grants/contracts: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD; honoraria: Astra Zeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, PharmaMar, Seagen, ESAI, Novartis; travel/accommodation/expenses: Roche, GSK, Astra Zeneca, PharmaMar, MSD; Data Safety Monitoring Board/Advisory Board: Clovis, Deciphera, AdaptImmune, Sutro, Immunogen. GS: grants: MSD Italia S.r.l; consulting fees: Tesaro Bio Italy S.r.l, Johnson & Johnson; payment for expert testimony: Clovis Oncology Italia S.r.l; NC: grants: GSK, Astrazeneca; consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche; honoraria: AstraZeneca, Novartis, Clovis Oncology,GSK, MSD/Merck; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche. AO: Grants to institution: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc., Eisai Ltd, F. Hoffmann-La Roche Ltd, Regeneron Pharmaceuticals, lmmunogen Inc, Merck, Sharp & Dohme de Esparsia SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; consulting fees and honoraria: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, lmmunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; travel/accommodation/expenses: AstraZeneca, PharmaMar, Roche; Data Safety Monitoring Board/Advisory Board: AstraZeneca, Clovis Oncology, Deciphera, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, MSD de Esparia SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, Sattucklabs, Itheos, Eisai; JS: study funding to institution: GSK, AstraZeneca, MSD, Clovis, Tesaro; consulting fees: GSK, Astra Zeneca, Tesaro, MSD, Elisei, Clovis, Riemser, Roche; travel/accomodation/expenses: Roche; Data Safety Monitoring Board/Advisory Board: GSK, PharmaMar, Novocure, Astra Zeneca, Clovis, GSK, Tesaro; ESGO Faculty; NOGGO President; PARSGO President. KL: grants: GSK; honoraria: Eisai; Data Safety Monitoring Board/Advisory Board: Eisai, MSD, Nycode, Astra Zeneca, GSK. CL: honoraria: IMSD, GSK, Eisai, Clovis Oncology; travel/accommodation/expenses: MSD, GSK; Data Safety Monitoring Board/Advisory Board: GSK. ME: stock/stock options: GSK. AdB: honoraria: Zodiac, AMGEN, GSK/Tesaro; Data Safety Monitoring Board/Advisory Board: AstraZeneca/MSD, AMGEN, Pfizer, GSK/Tesaro. All other authors declare no competing interests., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)