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Analysis of HIV-1 based lentiviral vector particle composition by PacBio long-read nucleic acid sequencing
Get PDFSupplementary Material is available online at https://www.liebertpub.com/doi/suppl/10.1089/hum.2024.121/suppl_file/hum.2024.121_supplementary_tables1.pdf (file: 175.92 KB) and https://www.liebertpub.com/doi/suppl/10.1089/hum.2024.121/suppl_file/hum.2024.121_supplementary_tables2.pdf (file: 101.70 KB).Lentivirus (LV) vectors offer permanent delivery of therapeutic genes to the host through an RNA intermediate genome. They are one of the most commonly used vectors for clinical gene therapy of inherited disorders such as immune deficiencies and cancer immunotherapy. One of the most difficult challenges facing their widespread application to patients is the large-scale production of highly pure vector stocks. To improve vector production and downstream purification, there has been a recent investment in the United Kingdom to establish good manufacturing process (GMP)-licensed centers for manufacture and quality control. Other requirements for these vectors include their target cell specificity and tropism, how to regulate gene expression of the therapeutic payload and their potential side effects. Comprehensive detail on the full nucleic acid content of LV is unknown, even though they have entered clinical trials. With potential adverse effects in mind, it is important to identify these contents to assess their safety and purity. In this study, we used highly sensitive PacBio long-distance, next-generation sequencing of reverse-transcribed vector component RNA to investigate the nucleic acid composition of recombinant HIV-1 particles generated by human 293T packaging cells. In this article, we describe our findings of nucleic acids other than the recombinant vector genome that exist, which could potentially be delivered during gene transfer, and suggest that removal of these unwanted components be considered before clinical LV application.Medical Research Council project: Crack It: A human IPS cell model for gene therapy vector safety evaluation Phase 2. The authors would like to thank Centre for Genomic Research, University of Liverpool, for the PacBio sequencing service platform used in this study and a GlaxoSmithKline (GSK) studentship funding award
Effectiveness of obesity interventions in sub-Saharan Africa: a systematic review and meta-analyses
Get PDFData Availability: All relevant data are within the manuscript and its Supporting Information files.Supporting information is available online at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0323717#sec018 .The escalating obesity epidemic in sub-Saharan Africa is a pressing regional concern. Despite this, there is scarce evidence of effective strategies to halt its upward trend in the region. We have, therefore, synthesised evidence on effective interventions to prevent and manage obesity in sub-Saharan Africa. We searched Scopus, PsycINFO, Cochrane Library, Web of Science and Medline for pertinent studies for this review. Studies were eligible if they focused on a sub-Saharan African country and assessed obesity/overweight with objective outcome measures. We examined their methodological quality with the Joanna Briggs Institute and the National Institutes of Health appraisal checklists. Publication bias was assessed with funnel plots. A meta-analysis with a random-effects model was fitted to explore the pooled effect of identified obesity interventions on anthropometric obesity measures. The heterogeneity of the studies was assessed using the I-square statistic. Our search yielded seven eligible studies for this review. Their quality ranged from moderate to high. The interventions identified included aerobic and resistance exercises, micronutrient supplementation and physical education. The meta-analysis revealed that aerobic and resistance training could significantly reduce obesity by approximately 34% (p = 0.04; 95%CI = -0.67 – -0.02). However, they do not significantly reduce waist circumference (Effect size = -1.14; 95%CI = -0.67–0.55; p = 0.19). Aerobic and resistance training exercises could be embedded in physical activity interventions to prevent and manage overweight and obesity in sub-Saharan Africa. PROSPERO registration number: CRD42023430503The author(s) received no specific funding for this work
Development and optimization of a photoautotrophic phycoerythrin production process
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The experimental data underlying this work have been uploaded here: https://doi.org/https://doi.org/10.17633/rd.brunel.25880428.v1.Acknowledgements:
The authors would like to acknowledge the excellent technical team at Brunel University London in particular Mr. Paul Josse, Mr. Paul Barrett, Mr. William Pierce and Mr. William Schkzamian for their assistance in constructing the photobioreactors.Supplementary Information is available onlineat: https://link.springer.com/article/10.1007/s10811-025-03524-x#Sec9 .Phycoerythrin is a pink pigment produced by photosynthetic microorganisms which has potential to be used as a sustainable colorant in the food, cosmetics and textile industries. In order for this to happen it is necessary to identify suitable strains for large-scale production and develop and optimize production processes. Relatively few species of red algae have been evaluated for their biotechnological potential and to address this gap this work examined five different species of red algae and three cyanobacteria to identify the most suitable candidates for phycoerythrin production. Results from initial screening experiments found a wide range of specific phycoerythrin contents (0.75–28 mg g−1). The four most promising species (Porphyridium purpureum, Rhodella violacea, Timspurckia oligopyrenoides and Flintiella sanguinaria) were grown in 3-L photobioreactors; of the species examined it was found that P. purpureum and R. violacea had the highest growth rate (approximately 0.6 day^−1). As part of the scale-up process it was found that ensuring sufficient nitrate was available in the medium was key in maintaining a high specific phycoerythrin content, with maximum values being 170 ± 34 mg g^−1 for P. purpureum and 120 ± 60 mg g^−1 for R. violacea. Increasing the applied light intensity led to increases in the cell density (to a maximum of 3.46 ± 0.36 g L^−1 for P. purpureum), while the specific phycoerythrin content was generally constant. Applying these insights led to a final volumetric phycoerythrin concentration of 360 ± 37 mg L^−1 for P. purpureum this being a 50-fold improvement over the original values. Results from this work provide valuable data about the growth and phycoerythrin productivity of diverse species of red algae as well as providing valuable insights into how the phycoerythrin production can be optimized.Not applicable
Orange Peel Waste Valorization: An Integrated Assessment of Environmental and Economic Sustainability in Animal Feed Production
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The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information file. Should any raw data files be needed in another format they are available from the corresponding author upon reasonable request.Supplementary Information is available online at: https://link.springer.com/article/10.1007/s12649-025-03044-2#Sec19 .This study examines the environmental and economic sustainability of producing a feed ingredient from waste orange peels (OP), for use in animal feed, focusing on two waste valorization strategies: one involving hydrolyzed and the other non-hydrolyzed OP. Life cycle assessment (LCA) and life cycle costing (LCC) methodologies were employed to assess the environmental impacts and economic feasibility. LCA data were derived from lab-scale experiments and existing literature, using the ReCiPe 2016 (H) method to quantify environmental impacts per tonne of animal feed. Key findings show that hydrolyzing OP results in higher impacts compared to non-hydrolyzed variant, primarily due to the saccharification-hydrolysis process, though this difference becomes negligible at the animal feed production stage. Sensitivity analysis reveals that variations in input materials, except for transport distance—particularly for the non-hydrolyzed variant—have limited effects on LCA outcomes. Comparisons with business-as-usual scenarios (landfilling, composting and incineration) show that while waste valorization reduces environmental impacts, it does not surpass incineration due to energy recovery potential. LCC analysis indicates that producing non-hydrolyzed feed ingredient is significantly more cost-effective than the hydrolyzed variant. Overall, the LCA and LCC results suggest that while OP waste valorization offers notable environmental benefits, non-hydrolyzed feed ingredient production is the more economically viable option, contributing to sustainable feed production. This study highlights the importance of integrating both environmental and economic considerations in waste valorization strategies and provides guidance for waste management companies and animal feed manufacturers to support circular economy practices.This paper is supported by the PRIMA program under grant agreement No. 2013, project NEWFEED. The PRIMA program is supported by the European Union
Rational synthesis of sea urchin-like NiCo-LDH/tannin carbon microsphere composites using microwave hydrothermal technique for high-performance asymmetric supercapacitor
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The data that support the findings of this study are available from the corresponding authors upon reasonable request.In this study, tannin-derived porous carbon (TAC) with different microstructures was prepared via a microwave hydrothermal method, followed by KOH activation. Subsequently, the sea urchin–like NiCo-LDH/Tannin-derived carbon-based microsphere composite materials were rationally synthesized through a single-step microwave hydrothermal co-assembly process. The physicochemical characteristics and supercapacitive performance were systematically analyzed. TAC with a microspherical structure promoted and controlled the growth of LDHs, resulting in a more regular sea urchin–like structure, improved dispersibility, reduced resistance, and increased active sites. NiCo-LDH@TAC600-0 (without KOH activation) as an electrode material delivered a specific capacitance (Cs) of 1250 F g^−1 at 1 A g^−1 and 1035 F g^−1 at 10 A g^−1, with a rate performance of 82.8%. The asymmetric supercapacitor device using NiCo-LDH@TAC600-0 and TAC provided an energy density of 30.8 Wh kg^−1 at 800 W kg^−1 and a capacitance retention rate of 72.5% after 5000 cycles. This study offers a novel approach to enhancing NiCo-LDH properties for efficient energy storage.The authors received financial support for this work from the National Natural Science Foundation of China (Grants 32071688), the central government guides local funds for scientific and technological development (2023L3044), Fujian Agriculture and Forestry University Science and Technology innovation special fund project (Grants KFB23142 and KFB24010), and the Innovative training program for college students of FAFU (Grants 202410389342)
Long-Run Trends and Cycles in US House Prices
Get PDFJEL Classification: C15; C22; E30.This paper analyses US nominal house prices at an annual frequency over the period from 1927 to 2022 by means of a very general time series model. This includes both a (linear and non-linear) deterministic and a stochastic component, with the latter allowing for fractional orders of integration at both the long-run and the cyclical frequencies. The results are heterogeneous depending on the model specification and on whether or not the series have been logged. Specifically, a linear model appears to be more appropriate for the logged data whilst a non-linear one appears to be a better fit for the original ones. Further, the order of integration at the zero or long-run frequency is much higher than at the cyclical one. The former is in fact around 1 in all specified models, which implies a high degree of persistence of this component. Finally, the order of integration of the cyclical structure implies that cycles have a periodicity of about 8 years, but it is almost insignificant in all cases.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.
Prof. Luis A. Gil-Alana gratefully acknowledges financial support from the project from ‘Ministerium de Economía, Industria y Competitividad’ (MINEIC), ‘Agencia Estatal de Investigación’ (AEI) Spain and ‘Fondo Europeo de Desarrollo Regional’ (FEDER), Grant D2023-149516NB-I00 funded by MCIN/AEI/ 10.13039/501100011033. He also acknowledges support from an internal Project of the Universidad Francisco de Vitoria
Introduction to the Research Handbook on the International Court of Justice
No full textThis Research Handbook presents an in-depth examination of the International Court of Justice (ICJ) and its jurisprudence. Contributing authors dissect the global governance functions of the ICJ and its impact on national legal orders worldwide.This project was funded by the CaPE Project, Marie Skłodowska-Curie Actions, grant agreement number 708228, Horizon 2020
Test-retest reliability of TMS motor evoked responses and silent periods during explosive voluntary isometric contractions
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The data collected and analysed during this study are available from the corresponding author upon reasonable request.Supplementary Information is available online at: https://link.springer.com/article/10.1007/s00421-025-05707-3#Sec21 .Purpose:
This study assessed the test–retest reliability of TMS motor evoked potentials (MEPs) and silent periods at early, middle, and late phases of the rising time–torque curve during explosive voluntary contractions. We also investigated how the number of consecutively averaged measurements influenced reliability.
Methods:
On two separate occasions 3–7 days apart, 14 adults performed several isometric explosive (1-s) contractions of the knee extensors, some of which were superimposed with TMS to elicit MEPs in the superficial quadriceps. Of those with TMS, stimulation was timed to elicit MEPs at either 45 (early), 115 (middle), or 190 ms (late) following contraction onset (16 with-TMS contractions per time condition). TMS was also superimposed at the plateau of 15 separate MVCs. Test–retest intraclass correlation coefficient (ICC) and coefficient of variation (CV) were calculated for MEPs and silent periods consecutively averaged over 3 to 15 separate contractions.
Results:
No one condition/phase was more reliable than another. For MEP amplitude, in all conditions except the explosive late phase, ICCs generally increased, and CV decreased, with an increase in the number of averaged contractions, and were > 0.50 ICC and 0.50 ICC and < 10% CV.
Conclusion:
Test–retest reliability of TMS responses is comparable between phases of explosive contraction and at the plateau of MVC. To maximise reliability of MEPs during explosive contractions or MVCs, we recommend future studies average data across more than the 3–5 contractions typically reported in the literature investigating MEPs at MVC plateau
Child Sexual Abuse and Family Court Proceedings
Get PDFCases involving child sexual abuse (CSA) allegations are among the most sensitive that the family courts encounter. Yet there is an absence of research and discussion on how CSA is responded to in the family court system, especially in private law proceedings
Determining the minimum important differences for field walking tests in adults with long-term conditions: a systematic review and meta-analysis
Get PDF• Correction - https://publications.ersnet.org/content/errev/34/176/245198• Supplementary material - https://publications.ersnet.org/content/errev/34/176/240198/DC1/embed/inline-supplementary-material-1.pdfIMPORTANCE: The minimum important difference (MID) for field walking tests aims to improve interpretation of outcomes, but the volume and heterogeneity of MIDs for these tests is challenging. We aimed to determine the MID for the 6-min walk distance (6MWD), incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT) in adults with long-term conditions. METHODS: This systematic review included studies that generated a MID using an anchor-based approach in patients with long-term conditions for the 6MWD, ISWT or ESWT field walking tests. Studies were screened and data extracted by independent reviewers. Meta-analyses were performed using RevMan. RESULTS: 42 studies were included in the analyses, involving n=13 949 participants. Of these, 12 studies involving exercise as an intervention were included in the meta-analyses to produce MIDs, presented as mean (95% confidence interval). The MID for the 6MWD was 25 m (24-26 m) for respiratory conditions, 23 m (8-37 m) for cardiac conditions and 37 m (26-49 m) for neurological/musculoskeletal conditions. The MID for the ISWT was 48 m (39-57 m) for respiratory conditions and 70 m (55-85 m) for cardiac conditions. The MID for ESWT in COPD was 159 s (94-224 s). The pooled MID across conditions within exercise interventions was 26 m (22-40 m) for the 6MWD and 53 m (44-62 m) for the ISWT, with reasonable heterogeneity (I2=48% and I2=47%, respectively). CONCLUSION: We propose new MIDs for exercise interventions using anchor-based methodology in long‑term conditions for the 6MWD, ISWT and ESWT. These can be used internationally for meta‑analyses where studies have used different field walking tests, to optimise trial sample size calculations, and for clinical service benchmarking
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