Symbiotic control of the olive fruit fly, Bactrocera oleae

The olive fruit fly Bactrocera oleae (Rossi) (OLF) is a major pest, which causes severe yield losses and quality decay of olive oil. The widespread use of chemical insecticides to control this pest is a major concern for the resulting environmental impact and food safety issues. Therefore, the development of sustainable control strategies is highly desirable. The primary endosymbiotic bacterium of the OLF, “Candidatus Erwinia dacicola”, is essential for successful larval development in unripe olive fruits. Then, targeting this endosymbiont with antimicrobial compounds may exert a control action against OLF. Here we evaluate the impact on OLF endosymbiont of Copper Oxychloride (CO) and the fungal metabolites Viridiol and Harzianic Acid (HA) produced by two biocontrol strains of Trichoderma spp. Laboratory bioassays were carried out on OLF wild populations to assess the effect of the oral administration of these compounds on mortality and fecundity of adult flies, and on larval development of their progeny in unripe olive fruits. Treated females were processed by qPCR to measure the endosymbiont load in the oesophageal bulb and in the midgut. Exposure to Viridiol and HA had a strong negative impact on endosymbiont load and OLF larval survival, while CO negatively affected both adults and larval stages, showing a combined toxic action and an anti-symbiotic effect, which was dose-dependent. These results provide new insights on the symbiotic control of the OLF and pave the way for developing new strategies based on the use of natural compounds with antimicrobial activity

Multi-parallel-task Time-delay Reservoir Computing combining a Silicon Microring with WDM

We numerically demonstrate a microring-based time-delay reservoir computing scheme that simultaneously solves three tasks involving time-series prediction, classification, and wireless channel equalization. Each task performed on a wavelength-multiplexed channel achieves state-of-the-art performance with optimized power and frequency detuning.Comment: 3 pages, 2 figures, Submitted to Optical Fiber Communication Conference (OFC) 202

Impact of Free-carrier Nonlinearities on Silicon Microring-based Reservoir Computing

We quantify the impact of thermo-optic and free-carrier effects on time-delay reservoir computing using a silicon microring resonator. We identify pump power and frequency detuning ranges with NMSE less than 0.05 for the NARMA-10 task depending on the time constants of the two considered effects.Comment: 2 pages, 2 figures. Submitted to IEEE Photonics Conference 202

Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens

Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4+ and CD8+ T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. OBJECTIVES: We evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DESIGN: A multicenter, randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Malnourished and sarcopenic men and women, 65 years and older (n = 330). INTERVENTION: A 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MEASUREMENTS: Isokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s-1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg-1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [ CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. CONCLUSION: ONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Femoral tunnel in revision anterior cruciate ligament reconstruction

The failure rate after anterior cruciate ligament (ACL) reconstruction performed by expert surgeons is estimated to be in the range of 10-15%, and only 60% of patients undergoing this surgery are able to resume sporting activities comparable to those they engaged in prior to the traumatic incident. Incorrect femoral tunnel placement is one of the main causes of failed ACL reconstruction and this must be remembered when undertaking revision surgery. There are various possible errors that can be committed and, to plan revision surgery correctly, it is fundamental to study the position of the existing femoral tunnel(s) both on classic anteroposterior and lateral plain radiographs and on computed tomography scans with frontal, sagittal, and coronal sections, and also using three-dimensional reconstruction. In-depth anatomical knowledge and familiarity with the various possible surgical techniques are also mandatory for a successful surgical outcome

Symbiosis disruption in the olive fruit fly, Bactrocera oleae (Rossi), as a potential tool for sustainable control

International audienceBACKGROUND: The olive fruit fly Bactrocera oleae (Rossi) (OLF) is a major agricultural pest, whose control primarily relies on the use of chemical insecticides. Therefore, development of sustainable control strategies is highly desirable. The primary endo-symbiotic bacterium of OLF, 'Candidatus Erwinia dacicola', is essential for successful larval development in unripe olive fruits. Therefore, targeting this endosymbiont with antimicrobial compounds may result in OLF fitness reduction and may exert control on natural populations of OLF.RESULTS: Here, we evaluate the impact of compounds with antimicrobial activity on the OLF endosymbiont. Copper oxychlor-ide (CO) and the fungal metabolite viridiol (Vi), produced by Trichoderma spp., were used. Laboratory bioassays were carried out to assess the effect of oral administration of these compounds on OLF fitness and molecular analyses (quantitative polymer-ase chain reaction) were conducted to measure the load of OLF-associated microorganisms in treated flies. CO and Vi were both able to disrupt the symbiotic association between OLF and its symbiotic bacteria, determining a significant reduction in the endosymbiont and gut microbiota load as well as a decrease in OLF fitness. CO had a direct negative effect on OLF adults. Conversely, exposure to Vi significantly undermined larval development of the treated female's progeny but did not show any toxicity in OLF adults.CONCLUSIONS: These results provide new insights into the symbiotic control of OLF and pave the way for the development of more sustainable strategies of pest control based on the use of natural compounds with antimicrobial activity