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Flux Sampling Suggests Metabolic Signatures of High Antibody-Producing CHO Cells
No full textChinese hamster ovary (CHO) cells remain the industry standard for producing numerous therapeutic proteins, particularly monoclonal antibodies (mAbs). However, achieving higher recombinant protein titers remains an ongoing challenge and a fundamental understanding of the cellular mechanism driving improved bioprocess performance remains elusive. To directly address these challenges and achieve substantial improvements, a more in-depth understanding of cellular function within a bioprocess environment may be required. Over the past decade, significant advancements have been made in the building of genome-scale metabolic models (GEMs) for CHO cells, bridging the gap between high information content 'omics data and the ability to perform in silico phenotypic predictions. Here, time-course transcriptomics has been employed to constrain culture phase-specific GEMs, representing the early exponential, late exponential, and stationary/death phases of CHO cell fed-batch bioreactor culture. Temporal bioprocess data, including metabolite uptake and secretion rates, as well as growth and productivity, has been used to validate flux sampling results. Additionally, high mAb-producing solutions have been identified and the metabolic signatures associated with improved mAb production have been hypothesized. Finally, constraint-based modeling has been utilized to infer specific amino acids, cysteine, histidine, leucine, isoleucine, asparagine, and serine, which could drive increased mAb production and guide optimal media and feed formulations.</p
Do Influential Articles on the Genetics of Autism Show Evidence of Engagement With the Autistic Community?
No full textCONSORT 2025 statement: updated guideline for reporting randomised trials
No full textWell designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent
Prodexchange:Digital-industrial economization in Google Search supply chain
No full textUsing Google as a case study, this paper analyzes the online advertising sector’s search industry. Arguing that search engines are not engines, it examines Google Search as a supply chain composed of five nodes: Crawler, Indexer, Ranker, Publisher, and Data Center. The final product of this chain is the search service presented to Google consumers, complete with ads and ancillary information. Empirically showing that production and exchange are one economic process in most of these supply chain nodes, we argue that treating them separately is neither accurate for description nor feasible for theory. In reality Google Search produces and exchanges simultaneously. We observe that the social sciences lack an approach to analyze such unitary production/exchange relations in computational industries. Addressing this blind spot, the paper offers an alternative to describe how the search industry works by bridging supply chain literature in management and the economization approach in sociology. We introduce the digital-industrial economization approach to analyze Google Search’s supply chain, in which a variety of nodes concurrently produce, exchange, barter, maintain, and/or store search products and their inputs. We present the term Prodexchange to characterize these novel integrated production/exchange combinations
Persistent dysoxia in very shallow seas across the Late Cambrian SPICE Event, Durness Group, UK
Get PDFThe global late Cambrian Steptoean Positive Isotopic Carbon Excursion (SPICE; ca. 495−492 Ma) has been linked to oceanic anoxia followed by a pulse of atmospheric oxygenation that in turn may have facilitated the Ordovician Radiation. To provide new insight into the evolution of very-shallow-water redox conditions across the SPICE, we present an integrated multiproxy study of carbonate rocks from the Durness Group, Scotland, UK, combining Fe speciation, redox-sensitive trace element systematics, and I/(Ca + Mg) ratios. We interpret the Durness SPICE peak to have occurred during an early highstand interval, where shallow waters were impacted by either regional mobilization of Fe2+ under low-oxygen conditions or episodic upwelling of deep, ferruginous, anoxic waters that followed high-frequency cycles. Unlike other records, our data show that very low marine oxygen concentrations (dysoxia) persisted before, during, and after the SPICE, confirming that a very shallow redoxcline was maintained in this region, with no evidence for any sustained increase in oxygenation. We conclude that under the prevailing low-atmospheric-oxygen conditions of the Cambrian, dysoxia was prevalent even in very shallow waters
Considering durability in carbon dioxide removal strategies for climate change mitigation
Get PDFThis Perspective describes the various dimensions of Carbon Dioxide Removal (CDR) durability and interprets them in the context of current policy making. Durability – together with scalability and sustainability – is an essential condition of CDR. It depends on (i) the duration of CO2 storage and (ii) the risk of reversing such storage. The risk profile of durability varies widely across CDR methods. Because engineered, novel CDR methods involve more stable forms of CO2 storage than nature-based CDR, these methods are often promoted as a priority for CDR mitigation investments. However, shorter-term CDR plays an essential role in balancing sources and sinks of greenhouse gases in the second half of this century. Decision makers must also consider CDR policies in a larger context that takes into account readiness and feasibility, policy alignment and co-benefits of different CDR methods. They must also address durability in CDR policies and contracts, which tend to span much shorter timeframes than those contemplated by science when discussing durability. We argue that nature-based conventional CDR and novel engineered CDR that show complementary timing and risk profiles can be deployed in synergistic CDR portfoliosto balance the conditions of durability, feasibility and social and environmental sustainability
Effectiveness and safety data on intravenous ferric derisomaltose for iron deficiency anaemia management in paediatric gastroenterology patients: a multicentre retrospective cohort study
Get PDFObjective: Iron deficiency anaemia is common in paediatric gastroenterology with intravenous iron increasingly utilised. While adult data are published for ferric derisomaltose (FDI), no paediatric data exist. Our aim was to assess the effectiveness and safety profile of FDI in paediatric gastroenterology.Design: Retrospective cohort study.Setting: Two UK referral centres (Edinburgh and Sheffield).Patients: All paediatric gastroenterology patients who received FDI from 6/2020 to 6/2023.Main outcome measures: Haematological and biochemical parameters were collected before and at 1, 3, 6 and 12 months after treatment, when available, together with the need for repeated FDI infusions and FDI adverse events.Results: Sixty-five patients were identified (54% male; median age 12.8 years, IQR 9.6–15.2), receiving 78 FDI infusions. After a single infusion 38/59 (64%) patients (effectiveness analysis) completely corrected their anaemia and 6/59 (10%) improved from moderate-severe to mild anaemia. Median haemoglobin increased from 92 (IQR 85-108) to 126 (IQR 115-132) g/L at 1 month (p<0.001) and peaked at 12 months (134g/L, IQR 125-142; p<0.001) post-infusion. A second infusion was performed in 12/59 (20%) patients with 9/12 correcting their anaemia. No significant biochemical alterations, including hypophosphatemia, were detected. Overall, 4/65 (6%) patients (safety analysis) experienced adverse events, with 3 discontinuing FDI infusion.Conclusions: Our real-world data reveal FDI is rapidly and persistently effective in correcting IDA in paediatric gastroenterology. No significant biochemical alterations or new safety signals were identified
Challenges of translational education research:Teachers’ interpretations of embodied learning
Get PDFThis paper addresses growing calls to address research-to-practice gaps by critically examining ways in which practitioners actively filter, interpret, re-purpose and enact research messages in their context, and the implications for developing translational resources. Analysis drew upon in-depth semi-structured interviews with ten teachers across the UK involved in three online workshops designed from both embodied learning research and STEM teacher educator expertise. Through a grounded theory approach, thematic analysis revealed three tensions in how teachers interpreted and enacted research messages in their practice: (1) extent to which ideas were seen as novel or pre-existing (less impression; more relatable), (2) value of resources (immediate appeal; potential message distortion), and (3) complexities of integrating practitioner insight into messages. The paper proposes ways these tensions might be navigated by contributing two additional guidelines for translation frameworks: (i) early exploration of existing perceptions and priorities for different audiences of translation, and (ii) early consideration of how messages can translate to accessible translational resources that can scale impact. The paper advocates greater researcher involvement in the development of these resources requiring ongoing consideration of how research messages are interpreted differently across audiences.</p
Decoding the genetic and environmental forces in propelling the surge of early-onset colorectal cancer
Get PDFEarly-onset colorectal cancer (EOCRC) shows a different epidemiological trend compared to later-onset colorectal cancer, with its incidence rising in most regions and countries worldwide. However, the reasons behind this trend remain unclear. The etiology of EOCRC is complex and could involve both genetic and environmental factors. Apart from Lynch syndrome and Familial Adenomatous Polyposis, sporadic EOCRC exhibits a broad spectrum of pathogenic germline mutations, genetic polymorphisms, methylation changes, and chromosomal instability. Early-life exposures and environmental risk factors, including lifestyle and dietary risk factors, have been found to be associated with EOCRC risk. Meanwhile, specific chronic diseases, such as inflammatory bowel disease, diabetes, and metabolic syndrome, have been associated with EOCRC. Interactions between genetic and environmental risk factors in EOCRC have also been explored. Here we present findings from a narrative review of epidemiological studies on the assessment of early-life exposures, of EOCRC-specific environmental factors, and their interactions with susceptible loci. We also present results from EOCRC-specific genome-wide association studies that could be used to perform Mendelian randomization analyses to ascertain potential causal links between environmental factors and EOCRC.</p
Investigation of a potential link between UK equestrians’ understanding of learning theory, and their perception of and response to a problematic equine behaviour
Get PDFPrevious studies have demonstrated poor understanding of learning theory amongst equine professionals, but further work is required to gauge the level of understanding within the general equestrian population. How equestrians’ understanding of learning theory affects their perception of problematic horse behaviour, and strategies used to deal with it, are also unknown. Therefore, the aim of this study was to investigate the level of understanding of learning theory amongst the general equestrian population, and to explore how this relates to the way equestrians perceive and respond to a problem behaviour. An online questionnaire was completed by 672 UK equestrians, aged > 18 years old, who had owned/loaned a horse for over 1 year. The results indicate that UK equestrians have a poor understanding of learning theory; only 16 % of respondents correctly identified all four quadrants of operant conditioning from example scenarios. Equestrians with a poorer understanding of learning theory were significantly (P < 0.001) more likely to consider two scientifically implausible motivators (i.e. horse testing rider and horse dominating rider) as possible explanations as to why the horse in an example scenario was performing a problem behaviour (napping i.e. reluctance/refusal to move forwards as directed by the rider where the horse may plant its feet and/or only moves backwards or sideways in response to the cue to move forwards). Furthermore, equestrians with a poorer understanding of learning theory were more likely to use derogatory descriptors to describe the horse. Respondents who correctly identified only 1/4 quadrants of operant conditioning were significantly more likely to use the descriptors “naughty”, “cheeky” and “disrespectful” to describe the horse performing the problem behaviour in the example scenario (all P < 0.001). The use of derogatory descriptors to describe the napping horse was also significantly associated with an increased likelihood of using a punishment-based intervention to manage this behaviour (“naughty”, “cheeky”, “disrespectful”: all P < 0.001). The results of this study provide evidence for an association between a poor understanding of learning theory, blaming the horse for performing problematic behaviour, use of derogatory terms to describe problematic equine behaviour, and use of punishment in response to these behaviours. Further work is now required to establish if interventions to improve UK equestrians’ understanding of equine behavioural science would lead to improved horse welfare
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