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Abstract Many epidemiological models and algorithms are used to fit the parameters of a given epidemic curve. On many occasions, fitting algorithms are interleaved with the actual epidemic models, which yields combinations of model-parameters that are hard to compare among themselves. Here, we provide a model-agnostic framework for epidemic parameter fitting that can (fairly) compare different epidemic models without jeopardizing the quality of the fitted parameters. Briefly, we have developed a Python framework that expects a Python function (epidemic model) and epidemic data and performs parameter fitting using automatic configuration. Our framework is capable of fitting parameters for any type of epidemic model, as long as it is provided as a Python function (or even in a different programming language). Moreover, we provide the code for different types of models, as well as the implementation of 4 concrete models with data to fit them. Documentation, code and examples can be found at https://ulog.udl.cat/static/doc/epidemic-gga/html/index.html .

Abstract Due to its high energy efficiency and environmental friendliness, solid-state cooling based on the barocaloric (BC) effect represents a promising alternative to traditional refrigeration technologies relying on greenhouse gases. Plastic crystals displaying orientational order-disorder solid-solid phase transitions have emerged among the most gifted materials on which to realize the full potential of BC solid-state cooling. However, a comprehensive understanding of the atomistic mechanisms on which order-disorder BC effects are sustained is still missing, and rigorous and systematic methods for quantitatively evaluating and anticipating them have not been yet established. Here, we present a computational approach for the assessment and prediction of BC effects in orientationally disordered materials that relies on atomistic molecular dynamics simulations and emulates quasi-direct calorimetric BC measurements. Remarkably, the proposed computational approach allows for a precise determination of the partial contributions to the total entropy stemming from the vibrational and molecular orientational degrees of freedom. Our BC simulation method is applied on the technologically relevant material CH3NH3PbI3 (MAPI), finding giant BC isothermal entropy changes (∣ΔS BC∣ ~ 10 J K−1 kg−1) under moderate pressure shifts of ~0.1 GPa. Intriguingly, our computational analysis of MAPI reveals that changes in the vibrational degrees of freedom of the molecular cations, not their reorientational motion, have a major influence on the entropy change that accompanies the order-disorder solid-solid phase transition.

Abstract Introduction Lebanon is a middle-income country facing substantial fragility features. Its health profile shows a high burden of NCD morbidity and mortality. This paper intends to analyse the political economy of NCD prevention and control in Lebanon. Methods This study adopted a literature-based case study research design using a problem-driven political economy analysis framework. A total of 94 peer-reviewed articles and documents from the grey literature published before June 2019 were retrieved and analysed. Results Lebanon’s political instability and fragile governance negatively affect its capacity to adapt a Health-in-All-Policies approach to NCD prevention and enable the blocking of NCD prevention policies by opposed stakeholders. Recent economic crises limit the fiscal capacity to address health financing issues and resulting health inequities. NCD care provision is twisted by powerful stakeholders towards a hospital-centred model with a powerful private sector. Stakeholders like the MOPH, UN agencies, and NGOs have been pushing towards changing the existing care model towards a primary care model. An incremental reform has been adopted to strengthen a network of primary care centres, support them with health technologies and improve the quality of primary care services. Nevertheless, outpatient services that are covered by other public funds remain specialist-led without much institutional regulation. Conclusion Our study revealed a locked equilibrium in NCD prevention policymaking in Lebanon, but with an incremental progress in service delivery reforms towards a primary care model. Advocacy and close monitoring by policy entrepreneurs (such as civil society) could initiate and sustain the implementation of policy change and care model reforms.

Abstract Objective To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real‐world setting. Methods The study is prospective and observational based on real‐world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone‐sensitive prostate cancer (mHSPC) and high‐risk non‐metastatic castration‐resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022. Results Of 227 patients treated with apalutamide, 10% had ECOG‐PS 2, and 41% were diagnosed with new‐generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment‐related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal‐therapies. Conclusions The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.

Abstract The detection of individual molecules and their dynamics is a long-standing challenge in the field of nanotechnology. In this work, we present a method that utilizes a nitrogen vacancy (NV) center and a dangling bond on the diamond surface to measure the coupling between two electronic targets tagged on a macromolecule. To achieve this, we design a multi-tone dynamical decoupling sequence that leverages the strong interaction between the nitrogen vacancy center and the dangling bond. In addition, this sequence minimizes the impact of decoherence finally resulting in an increased signal-to-noise ratio. This proposal has the potential to open up avenues for fundamental research and technological innovation in distinct areas such as biophysics and biochemistry.

ABSTRACTEuropean Territorial Cooperation programmes (also known as Interreg) are designed to promote integration by encouraging organizations in multiple regions to work together on projects to address shared challenges. While some key aspects of these programmes have been studied (territorial scope, thematic areas, types of initiatives), research into participant organizations and their logic within partnerships (groups of organizations working together on projects) and the reasons for their participation in multiple projects, individually or in clusters, has been less thorough. This article presents a quantitative analysis of programmes under Interreg B and C, investigating the variables that influence organizations’ involvement in partnerships and the logic behind repeated collaborations. The aim is to supplement existing research, complementing it and supporting providing a better understanding of this framework to programme planners, enabling them to make more informed decisions when aiming to maximize the impact of their programmes when considering partners and partnerships.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, and it is currently the seventh leading cause of death worldwide. It is characterized by the extracellular aggregation of the amyloid β-peptide (Aβ) into oligomers and fibrils that cause synaptotoxicity and neuronal death. Aβ exhibits a dual role in promoting oxidative stress and inflammation. This review aims to unravel the intricate connection between these processes and their contribution to AD progression. The review delves into oxidative stress in AD, focusing on the involvement of metals, mitochondrial dysfunction, and biomolecule oxidation. The distinct yet overlapping concept of nitro-oxidative stress is also discussed, detailing the roles of nitric oxide, mitochondrial perturbations, and their cumulative impact on Aβ production and neurotoxicity. Inflammation is examined through astroglia and microglia function, elucidating their response to Aβ and their contribution to oxidative stress within the AD brain. The blood–brain barrier and oligodendrocytes are also considered in the context of AD pathophysiology. We also review current diagnostic methodologies and emerging therapeutic strategies aimed at mitigating oxidative stress and inflammation, thereby offering potential treatments for halting or slowing AD progression. This comprehensive synthesis underscores the pivotal role of Aβ in bridging oxidative stress and inflammation, advancing our understanding of AD and informing future research and treatment paradigms.

A diamond-based sensor utilizing nitrogen-vacancy (NV) center ensembles permits the analysis of micron-sized samples through nuclear magnetic resonance (NMR) techniques at room temperature. Current efforts are directed towards extending the operating range of NV centers into high magnetic fields, driven by the potential for larger nuclear spin polarization of the target sample and the presence of enhanced chemical shifts. Especially interesting is the access to J-couplings as they carry information of chemical connectivity inside molecules. In this work, we present a protocol to access J-couplings in both homonuclear and heteronuclear cases with NV centers at high magnetic fields. Our protocol leads to a clear spectrum exclusively containing J-coupling features with high resolution. This resolution is limited primarily by the decoherence of the target sample, which is mitigated by the noise-filtering capacities of our method.

Water pricing is an economic instrument traditionally used to reduce water demand. However, its effective implementation requires knowledge of the extent to which users reduce water consumption with increasing water prices. The price elasticity of water demand has been estimated using econometric regression, which relies on cross-sectional and time-series water data. As an alternative, we propose the use of agent-based modelling, which does not require reliable historical data on water prices and consumption and enables the simulation of multiple scenarios with different consumer profiles, behaviour profiles and water price changes, thereby allowing comprehensive understanding of price elasticity estimates. To illustrate the potential use of agent-based modelling for the estimation of water demand price elasticity, we performed an empirical application to a residential area in Chile. Price elasticity estimates ranged from −0.0159 to −0.1036 (mean −0.0250), indicating that residential water consumption is inelastic to price changes. This result is consistent with previous findings. Agent-based modelling is an alternative for the ex-ante assessment of the potential effectiveness of water pricing policies intended to reduce residential water demand.

Muscle and bone tissues are interconnected, and both rely on an adequate protein intake. Recommendations for protein intake for older adults specifically vary across countries. The purpose of this narrative review is to discuss the existing evidence for protein recommendations for supporting muscle and bone health in older adults and to evaluate if a protein intake above the current population reference intake (PRI) for older adults would be scientifically justified. First, this review summarizes the protein recommendations from bodies setting dietary reference values, expert groups, and national health organizations. Next, relevant studies investigating the impact of protein on muscle and bone health in older adults are discussed. In addition, the importance of protein quality for muscle and bone health is addressed. Lastly, a number of research gaps are identified to further explore the added value of a protein intake above the PRI for older adults.

Background With the aim of improving treatment retention in patients with the onset of alcohol-related liver disease (ArLD), we designed a blended intervention (brief motivational intervention + ‘serious game’ (SG)). We present the participatory design methodology and outcomes and the usability assessment of the intervention. Methods (1) The design of the SG was based on the outcomes of two 3-h co-creation sessions with 37 participants (healthcare and technology professionals, patients, and patients’ relatives). The brief face-to-face motivational intervention was based on the 5 As Model and adapted to the ArLD population. (2) Usability pilot study: 20 participants (10 ArLD patients + 10 healthcare professionals) received the intervention. System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ) were applied to assess the SG usability and patients’ satisfaction with it. Weekly semi-structured interviews on the phone were conducted to identify the preferred elements in the SG and those aspects that should be improved. Results (1) Design: an SG in the form of a gamified web app, consisting of a daily activity for six weeks and adapted brief motivational interviewing. (2) Usability pilot study: usability results were excellent for both patients and healthcare professionals (SUS median score = 85). The general usability, the quality of the information provided by the SG and the quality of the interface were very positively rated in the PSSUQ (overall median score = 2, IQR = 1–2). The best-rated aspects were the provision of feedback, the use of metaphors and the application of audiovisual material. Changes in the design, response mechanics and content were applied after the study. Conclusions The usability and acceptability of an intervention for increasing retention to treatment in patients with recent onset of ArLD and AUD were excellent for patients and healthcare professionals. A randomized-controlled trial is required to test the efficacy of this approach.

BackgroundVirtual reality (VR) interventions, based on cognitive behavioral therapy principles, have been proven effective as complementary tools in managing obesity and have been associated with promoting healthy behaviors and addressing body image concerns. However, they have not fully addressed certain underlying causes of obesity, such as a lack of motivation to change, low self-efficacy, and the impact of weight stigma interiorization, which often impede treatment adherence and long-term lifestyle habit changes. To tackle these concerns, this study introduces the VR self-counseling paradigm, which incorporates embodiment and body-swapping techniques, along with motivational strategies, to help people living with obesity effectively address some of the root causes of their condition. ObjectiveThis study aims to assess the clinical efficacy of ConVRself (Virtual Reality self-talk), a VR platform that allows participants to engage in motivational self-conversations. MethodsA randomized controlled trial was conducted with 68 participants from the bariatric surgery waiting list from the obesity unit of the Vall d’Hebron University Hospital in Barcelona, Spain. Participants were assigned to 1 of 3 groups: a control group (CG), which only received treatment as usual from the obesity unit; experimental group 1 (EG1), which, after intensive motivational interviewing training, engaged in 4 sessions of VR-based self-conversations with ConVRself, and underwent embodiment and body-swapping techniques; and experimental group 2 (EG2), which engaged in 4 VR-based sessions led by a virtual counselor with a prerecorded discourse, and only underwent the embodiment technique. In the case of both EG1 and EG2, the VR interventions were assisted by a clinical researcher. Readiness to change habits, eating habits, and psychological variables, as well as adherence and satisfaction with ConVRself were measured at baseline, after the intervention, 1 week after the intervention, and 4 weeks after the intervention. ResultsRegarding the primary outcomes, EG1 (24/68, 35%) and EG2 (22/68, 32%) showed significant improvements in confidence to lose weight compared to the CG (22/68, 32%) at all assessment points (β=−.16; P=.02). Similarly, EG1 demonstrated a significant increase after the intervention in readiness to exercise more compared to the CG (β=−.17; P=.03). Regarding the secondary outcomes, EG1 participants showed a significant reduction in uncontrolled eating (β=.71; P=.01) and emotional eating (β=.29; P=.03) compared to the CG participants, as well as in their anxiety levels compared to EG2 and CG participants (β=.65; P=.01). In addition, participants from the experimental groups reported high adherence and satisfaction with the VR platform (EG1: mean 59.82, SD 4.00; EG2: mean 58.43, SD 5.22; d=0.30, 95% CI −0.30 to 0.89). ConclusionsThis study revealed that using VR self-conversations, based on motivational interviewing principles, may have benefits in helping people with obesity to enhance their readiness to change habits and self-efficacy, as well as reduce dysfunctional eating behaviors and anxiety. Trial RegistrationClinicalTrials.gov NCT05094557; https://www.clinicaltrials.gov/study/NCT05094557

In this study, the effectiveness of a selected strain of Metschnikowia pulcherrima (MP1) was compared to that of sulphur dioxide for preventing white grape must from browning. Sulphur dioxide was found to drastically reduce oxygen consumption rate, protect hydroxycinnamic acids against oxidation and prevent grape must from browning, even in the presence of laccase. By contrast, supplementation with the selected strain of Metschnikowia pulcherrima (MP1) drastically increased oxygen consumption rate, thus reducing the amount of oxygen available for polyphenol oxidases. In the absence of laccase, this resulted in a decrease in browning and a certain degree of protection of the hydroxycinnamic acids, but in the presence of laccase it was not effective enough. Consequently, the selected strain of Metschnikowia pulcherrima (MP1) can be considered an interesting alternative to sulphur dioxide for preventing browning in white grape must, but only in conditions of healthy grapes.

Background & Aims: Porto-sinusoidal vascular disorder (PSVD) encompasses a group of liver diseases with vascular abnormalities that can cause portal hypertension in the absence of cirrhosis. The new diagnostic criteria allow for coexistence with other liver diseases, however its relationship with chronic hepatitis B (CHB) remains unclear. This study aimed to assess HBV prevalence in a PSVD cohort and evaluate its clinical impact. Methods: This retrospective study was conducted on patients with PSVD at Hospital Clínic Barcelona. HBV serology was evaluated, and patients were categorized into HBV chronic infection, past infection, or no HBV exposure. Clinical characteristics and outcomes were compared. Results: We included 155 patients with PSVD. Prevalence of CHB and past HBV infection in patients with PSVD was higher than in the general population (5.8% vs. 0.5%, p

The hitherto unexplained reduction of cell-specific productivity in transient gene expression (TGE) at high cell density (HCD) is known as the cell density effect (CDE). It currently represents a major challenge in TGE-based bioprocess intensification. This phenomenon has been largely reported, but the molecular principles governing it are still unclear. The CDE is currently understood to be caused by the combination of an unknown inhibitory compound in the extracellular medium and an uncharacterized cellular change at HCD. This study investigates the role of extracellular vesicles (EVs) as extracellular inhibitors for transfection through the production of HIV-1 Gag virus-like particles (VLPs) via transient transfection in HEK293 cells. EV depletion from the extracellular medium restored transfection efficiency in conditions that suffer from the CDE, also enhancing VLP budding and improving production by 60%. Moreover, an alteration in endosomal formation was observed at HCD, sequestering polyplexes and preventing transfection. Overexpression of UDP-glucose ceramide glucosyltransferase (UGCG) enzyme removed intracellular polyplex sequestration, improving transfection efficiency. Combining EV depletion and UGCG overexpression improved transfection efficiency by ∼45% at 12 × 106 cells/mL. These results suggest that the interaction between polyplexes and extracellular and intracellular vesicles plays a crucial role in the CDE, providing insights for the development of strategies to mitigate its impact.

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.

This research study investigates the influence of demographic factors, including gender, position, and year of experience on perceptions of online learning success during the pandemic. The study acknowledges that various factors, such as prior experience with online learning, technological literacy, and cultural context, influenced the perception of human resources towards online learning. The study will utilize a quantitative research approach with surveys and statistical analysis to gather and analyze data from executives managing education programs in Thai private higher education institutions. The participants in the study were executives managing education programs working in Thai private higher education institutions, including deans, vice deans, assistant deans, heads of departments, assistants to department heads, and full-time lecturers. A sample group of 213 participants will be selected using simple random sampling. Data will be collected through surveys distributed electronically to the selected participants. The survey will consist of a validated questionnaire with good content validity and reliability. Quantitative research methods will be employed to analyze the gathered data, including multivariate statistics (ANOVA), to interpret the findings. The research findings from this study will contribute to the existing literature on online learning effectiveness by examining the role of demographic factors in shaping perceptions of success in the context of the pandemic. The findings have practical implications for educational institutions in designing and implementing online learning programs during the pandemic and beyond, considering the demographic characteristics of their participants. The study suggests that institutions should consider the effects of gender, position, and year of experience in shaping perceptions and behaviours related to online learning, provide targeted support, foster collaboration and knowledge sharing, conduct ongoing research and evaluation, and adopt a multi-dimensional approach to enhance the effectiveness of online learning initiatives. Further study and contextual considerations are necessary to understand demographic factors' effects on online learning perceptions comprehensively.

As the introduction to the 40th anniversary issue of Revista CIDOB d’Afers Internacionals, this paper looks at developments in international relations over the last four decades, alongside the publication’s content and against the backdrop of the current crisis of the international order (or disorder). It spans the end of the Cold War and the faith deposited in globalisation and liberal democracy in the unipolar world of the mid-1990s, taking in the spread of the values and ideas of global governance at the end of the last century, before arriving at the growing multipolarity, rivalry between China and the United States and the challenge to the liberal order and permacrisis of recent years. Special mention is made of the impact of the COVID-19 pandemic and Russia’s war in Ukraine.

Abstract Background Given the variability of intensive care unit (ICU) costs in different countries and the importance of this information for guiding clinicians to effective treatment and to the organisation of ICUs at the national level, it is of value to gather data on this topic for analysis at the national level in Belgium. The objectives of the study were to assess the total cost of ICUs and the factors that influence the cost of ICUs in hospitals in Belgium. Methods This was a retrospective cohort study using data collected from the ICUs of 17 Belgian hospitals from January 01 to December 31, 2018. A total of 18,235 adult ICU stays were included in the study. The data set was a compilation of inpatient information from analytical cost accounting of hospitals, medical discharge summaries, and length of stay data. The costs were evaluated as the expenses related to the management of hospital stays from the hospital’s point of view. The cost from the hospital perspective was calculated using a cost accounting analytical methodology in full costing. We used multivariate linear regression to evaluate factors associated with total ICU cost per stay. The ICU cost was log-transformed before regression and geometric mean ratios (GMRs) were estimated for each factor. Results The proportion of ICU beds to ward beds was a median [p25-p75] of 4.7% [4.4–5.9]. The proportion of indirect costs to total costs in the ICU was 12.1% [11.4–13.3]. The cost of nurses represented 57.2% [55.4–62.2] of direct costs and this was 15.9% [12.0-18.2] of the cost of nurses in the whole hospital. The median cost per stay was €4,267 [2,050–9,658] and was €2,160 [1,545–3,221] per ICU day. The main factors associated with higher cost per stay in ICU were Charlson score, mechanical ventilation, ECMO, continuous hemofiltration, length of stay, readmission, ICU mortality, hospitalisation in an academic hospital, and diagnosis of coma/convulsions or intoxication. Conclusions This study demonstrated that, despite the small proportion of ICU beds in relation to all services, the ICU represented a significant cost to the hospital. In addition, this study confirms that nursing staff represent a significant proportion of the direct costs of the ICU. Finally, the total cost per stay was also important but highly variable depending on the medical factors identified in our results.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as elemental analysis and HR-MS. The structure of an n-hexane monosolvate has been determined by single-crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677, and C. tropicalis ATCC 64677) has been tested using the disk diffusion and microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020–2023). Description: The implementation research approach involved a twelve-month pre-implementation period to assess feasibility and define the local action plans, followed by a sixteen-month implementation phase. During the two periods, a well-defined combination of experience-based co-design and quality improvement methodologies were applied. Discussion: The evolution of the Catalan HRA strategy (2010–2023) illustrates its potential for health systems transformation, as well as its transferability. The main barriers and facilitators for HRA adoption were identified. The report proposes a set of key steps to facilitate site customized deployment of HRA contributing to define a roadmap to foster large-scale adoption across Europe. Conclusions: Successful adoption of the AMG algorithm was achieved in the two sites confirming transferability. Marche identified the key requirements for a population-based HRA strategy, whereas Viljandi Hospital proved its potential for clinical use paving the way toward value-based healthcare strategies.

Summary: Platform trials bring the promise of making clinical research more efficient and more patient centric. While their use has become more widespread, including their prominent role during the COVID-19 pandemic response, broader adoption of platform trials has been limited by the lack of experience and tools to navigate the critical upfront planning required to launch such collaborative studies. The European Union-Patient-cEntric clinicAl tRial pLatform (EU-PEARL) initiative has produced new methodologies to expand the use of platform trials with an overarching infrastructure and services embedded into Integrated Research Platforms (IRPs), in collaboration with patient representatives and through consultation with U.S. Food and Drug Administration and European Medicines Agency stakeholders. In this narrative review, we discuss the outlook for platform trials in Europe, including challenges related to infrastructure, design, adaptations, data sharing and regulation. Documents derived from the EU-PEARL project, alongside a literature search including PubMed and relevant grey literature (e.g., guidance from regulatory agencies and health technology agencies) were used as sources for a multi-stage collaborative process through which the 10 more important points based on lessons drawn from the EU-PEARL project were developed and summarised as guidance for the setup of platform trials. We conclude that early involvement of critical stakeholder such as regulatory agencies or patients are critical steps in the implementation and later acceptance of platform trials. Addressing these gaps will be critical for attaining the full potential of platform trials for patients. Funding: Innovative Medicines Initiative 2 Joint Undertaking with support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

Abstract Stage‐based demographic methods, such as matrix population models (MPMs), are powerful tools used to address a broad range of fundamental questions in ecology, evolutionary biology and conservation science. Accordingly, MPMs now exist for over 3000 species worldwide. These data are being digitised as an ongoing process and periodically released into two large open‐access online repositories: the COMPADRE Plant Matrix Database and the COMADRE Animal Matrix Database. During the last decade, data archiving and curation of COMPADRE and COMADRE, and subsequent comparative research, have revealed pronounced variation in how MPMs are parameterized and reported. Here, we summarise current issues related to the parameterisation and reporting of MPMs that arise most frequently and outline how they affect MPM construction, analysis, and interpretation. To quantify variation in how MPMs are reported, we present results from a survey identifying key aspects of MPMs that are frequently unreported in manuscripts. We then screen COMPADRE and COMADRE to quantify how often key pieces of information are omitted from manuscripts using MPMs. Over 80% of surveyed researchers (n = 60) state a clear benefit to adopting more standardised methodologies for reporting MPMs. Furthermore, over 85% of the 300 MPMs assessed from COMPADRE and COMADRE omitted one or more elements that are key to their accurate interpretation. Based on these insights, we identify fundamental issues that can arise from MPM construction and communication and provide suggestions to improve clarity, reproducibility and future research utilising MPMs and their required metadata. To fortify reproducibility and empower researchers to take full advantage of their demographic data, we introduce a standardised protocol to present MPMs in publications. This standard is linked to www.compadre‐db.org, so that authors wishing to archive their MPMs can do so prior to submission of publications, following examples from other open‐access repositories such as DRYAD, Figshare and Zenodo. Combining and standardising MPMs parameterized from populations around the globe and across the tree of life opens up powerful research opportunities in evolutionary biology, ecology and conservation research. However, this potential can only be fully realised by adopting standardised methods to ensure reproducibility.

Abstract The analysis of pedestrian GPS datasets is fundamental to further advance on the study and the design of walkable cities. The highest resolution GPS data can characterize micro-mobility patterns and pedestrians’ micro-motives in relation to a small-scale urban context. Purposed-based recurrent mobility data inside people’s neighbourhoods is an important source in these sorts of studies. However, micro-mobility around people’s homes is generally unavailable, and if data exists, it is generally not shareable often due to privacy issues. Citizen science and its public involvement practices in scientific research are valid options to circumvent these challenges and provide meaningful datasets for walkable cities. The study presents GPS records from single-day home-to-school pedestrian mobility of 10 schools in the Barcelona Metropolitan area (Spain). The research provides pedestrian mobility from an age-homogeneous group of people. The study shares processed records with specific filtering, cleaning, and interpolation procedures that can facilitate and accelerate data usage. Citizen science practices during the whole research process are reported to offer a complete perspective of the data collected.

Abstract Polyphosphate (poly-P) biosynthesis in bacteria has been linked to many physiological processes and has been characterized as an interesting functional molecule involved in intestinal homeostasis. We determined the capacity for poly-P production of 18 probiotic strains mainly belonging to Bifidobacterium and former Lactobacillus genera, showing that poly-P synthesis varied widely between strains and is dependent on the availability of phosphate and the growth phase. Bifidobacteria were especially capable of poly-P synthesis and poly-P kinase (ppk) genes were identified in their genomes together with a repertoire of genes involved in phosphate transport and metabolism. In Bifidobacterium longum KABP042, the strain we found with highest poly-P production, variations in ppk expression were linked to growth conditions and presence of phosphate in the medium. Moreover, the strain produced poly-P in presence of breast milk and lacto-N-tetraose increased the amount of poly-P synthesized. Compared to KABP042 supernatants low in poly-P, exposure of Caco-2 cells to KABP042 supernatants rich in poly-P resulted in decreased epithelial permeability and increased barrier resistance, induction of epithelial protecting factors such as HSP27 and enhanced expression of tight junction protein genes. These results highlight the role of bifidobacteria-derived poly-P as a strain-dependent functional factor acting on epithelial integrity.

Background: Magnetic resonance imaging (MRI)-based risk calculators (MRI-RCs) individualise the likelihood of clinically significant prostate cancer (csPCa) and improve candidate selection for prostate biopsy beyond the Prostate Imaging Reporting and Data System (PI-RADS). Objective: To compare the Barcelona (BCN) and Rotterdam (ROT) MRI-RCs in an entire population and according to the PI-RADS categories. Design, setting, and participants: A prospective comparison of BCN- and ROT-RC in 946 men with suspected prostate cancer in whom systematic biopsy was performed, as well as target biopsies of PI-RADS ≥3 lesions. Outcome measurements and statistical analysis: Saved biopsies and undetected csPCa (grade group ≥2) were determined. Results and limitations: The csPCa detection was 40.8%. The median risks of csPCa from BCN- and ROT-RC were, respectively, 67.1% and 25% in men with csPCa, whereas 10.5% and 3% in those without csPCa (p

Abstract Machine learning (ML) could have advantages over traditional statistical models in identifying risk factors. Using ML algorithms, our objective was to identify the most important variables associated with mortality after dementia diagnosis in the Swedish Registry for Cognitive/Dementia Disorders (SveDem). From SveDem, a longitudinal cohort of 28,023 dementia-diagnosed patients was selected for this study. Sixty variables were considered as potential predictors of mortality risk, such as age at dementia diagnosis, dementia type, sex, body mass index (BMI), mini-mental state examination (MMSE) score, time from referral to initiation of work-up, time from initiation of work-up to diagnosis, dementia medications, comorbidities, and some specific medications for chronic comorbidities (e.g., cardiovascular disease). We applied sparsity-inducing penalties for three ML algorithms and identified twenty important variables for the binary classification task in mortality risk prediction and fifteen variables to predict time to death. Area-under-ROC curve (AUC) measure was used to evaluate the classification algorithms. Then, an unsupervised clustering algorithm was applied on the set of twenty-selected variables to find two main clusters which accurately matched surviving and dead patient clusters. A support-vector-machines with an appropriate sparsity penalty provided the classification of mortality risk with accuracy = 0.7077, AUROC = 0.7375, sensitivity = 0.6436, and specificity = 0.740. Across three ML algorithms, the majority of the identified twenty variables were compatible with literature and with our previous studies on SveDem. We also found new variables which were not previously reported in literature as associated with mortality in dementia. Performance of basic dementia diagnostic work-up, time from referral to initiation of work-up, and time from initiation of work-up to diagnosis were found to be elements of the diagnostic process identified by the ML algorithms. The median follow-up time was 1053 (IQR = 516–1771) days in surviving and 1125 (IQR = 605–1770) days in dead patients. For prediction of time to death, the CoxBoost model identified 15 variables and classified them in order of importance. These highly important variables were age at diagnosis, MMSE score, sex, BMI, and Charlson Comorbidity Index with selection scores of 23%, 15%, 14%, 12% and 10%, respectively. This study demonstrates the potential of sparsity-inducing ML algorithms in improving our understanding of mortality risk factors in dementia patients and their application in clinical settings. Moreover, ML methods can be used as a complement to traditional statistical methods.

Abstract Despite exponential growth in ecological data availability, broader interoperability amongst datasets is needed to unlock the potential of open access. Our understanding of the interface of demography and functional traits is well-positioned to benefit from such interoperability. Here, we introduce MOSAIC, an open-access trait database that unlocks the demographic potential stored in the COMADRE, COMPADRE, and PADRINO open-access databases. MOSAIC data were digitised and curated through a combination of existing datasets and new trait records sourced from primary literature. In its first release, MOSAIC (v. 1.0.0) includes 14 trait fields for 300 animal and plant species: biomass, height, growth determination, regeneration, sexual dimorphism, mating system, hermaphrodism, sequential hermaphrodism, dispersal capacity, type of dispersal, mode of dispersal, dispersal classes, volancy, and aquatic habitat dependency. MOSAIC includes species-level phylogenies for 1,359 species and population-specific climate data. We identify how database integration can improve our understanding of traits well-quantified in existing repositories and those that are poorly quantified (e.g., growth determination, modularity). MOSAIC highlights emerging challenges associated with standardising databases and demographic measures.

Stenotrophomonas maltophilia are ubiquitous Gram-negative bacteria found in both natural and clinical environments. It is a remarkably adaptable species capable of thriving in various environments, thanks to the plasticity of its genome and a diverse array of genes that encode a wide range of functions. Among these functions, one notable trait is its remarkable ability to resist various antimicrobial agents, primarily through mechanisms that regulate the diffusion across cell membranes. We have investigated the Mla ABC transport system of S. maltophilia, which in other Gram-negative bacteria is known to transport phospholipids across the periplasm and is involved in maintaining outer membrane homeostasis. First, we structurally and functionally characterized the periplasmic substrate-binding protein MlaC, which determines the specificity of this system. The predicted structure of the S. maltophilia MlaC protein revealed a hydrophobic cavity of sufficient size to accommodate the phospholipids commonly found in this species. Moreover, recombinant MlaC produced heterologously demonstrated the ability to bind phospholipids. Gene knockout experiments in S. maltophilia K279a revealed that the Mla system is involved in baseline resistance to antimicrobial and antibiofilm agents, especially those with divalent-cation chelating activity. Co-culture experiments with Pseudomonas aeruginosa also showed a significant contribution of this system to the cooperation between both species in the formation of polymicrobial biofilms. As suggested for other Gram-negative pathogenic microorganisms, this system emerges as an appealing target for potential combined antimicrobial therapies.

We study the $\overline {\mathbb {F}}_{p}$ -points of the Kisin–Pappas integral models of Shimura varieties of Hodge type with parahoric level. We show that if the group is quasi-split, then every isogeny class contains the reduction of a CM point, proving a conjecture of Kisin–Madapusi–Shin. We, furthermore, show that the mod p isogeny classes are of the form predicted by the Langlands–Rapoport conjecture (cf. Conjecture 9.2 of [Rap05]) if either the Shimura variety is proper or if the group at p is unramified. The main ingredient in our work is a global argument that allows us to reduce the conjecture to the case of very special parahoric level. This case is dealt with in the Appendix by Zhou. As a corollary to our arguments, we determine the connected components of Ekedahl–Oort strata.

This work compares the ancestral method for elaborating sparkling wines with the most widely used traditional method. Ancestral method is a single fermentation procedure in which the fermenting grape must is bottled before the end of alcoholic fermentation whereas traditional method involves a second fermentation of a base wine inside a bottle. Macabeo grapes were used to elaborate a traditional sparkling wine and two ancestral sparkling wines, one with a low yeast population and one with a high yeast population. The findings indicate that ancestral sparkling wines have lower ethanol content and can be elaborated using lower sulphur dioxide levels. In general, ancestral sparkling wines showed similar protein concentration, higher polysaccharide content, similar or better foamability (HM) than the traditional sparkling wine., No differences were found in the foam stability (HS). In addition, the sensory analysis indicated that ancestral sparkling wines have smaller bubble size, lower CO2 aggressivity, they seemed to have longer ageing time and were scored better than the traditional sparkling wine. These results therefore indicate that the ancestral method is of great interest for the elaboration of high-quality sparkling wines.

ObjectiveThis study aims to comprehend the impact of handball practice on sub-elite athletes by investigating transcriptomic changes that occur during a match. The primary focus encompasses a dual objective: firstly, to identify and characterize these transcriptomic alterations, and secondly, to establish correlations between internal factors (gene expression), and external loads measured through Electronic Performance and Tracking Systems (EPTS variables). Ultimately, this comprehensive analysis seeks to evaluate both acute and chronic responses to exercise within the context of handball training.MethodsThe study included sixteen elite male athletes from the FC Barcelona handball second team. Blood samples were extracted at three different time points: before the match at baseline levels (T1), immediately upon completion (T2), and 24 hours after completion (T3). Differential gene expression, Gene Ontology Term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in two comparisons: Comparison 1 (T1 vs T2) and Comparison 2 (T1 vs T3). Further, the correlation between gene expression levels and training variables (external load) was conducted.ResultsIn T1 vs T2, 3717 of the 14632 genes detected were differentially expressed (adjusted p-value < 0.05), and enrichment of terms related to the immune system, mitochondria, and metabolic processes was found. Further, significant linear correlations were obtained between High-Speed running (HSR) and high-intensity variables such as acceleration ACC and deceleration DEC values with amino acids, and inflammatory and oxidative environment-related pathways, both in chronic and acute response.ConclusionsThis research highlights the effects of external workload on elite athletes during a handball match and throughout the season. The study identifies deregulation in the immune system, mitochondrial functions, and various metabolic pathways during the match. Additionally, it establishes correlations between the external load and pathways associated with amino acids, inflammation, oxidative environment, and regulation. These findings offer insights into the immediate and chronic responses of athletes to physical effort.

The importance of patient centricity and keeping the patient at the heart of research design is now well recognised within the healthcare community. The involvement of patient, caregiver and clinician representatives in the study design process may help researchers to achieve this goal and to ensure robust and meaningful data generation. Real-world data collection allows for a more flexible and patient-centred research approach for gaining important insights into the experience of disease and treatments, which is acutely relevant for rare diseases where knowledge about the disease is more likely to be limited. Here, we describe a practical example of a patient-centric, multi-stakeholder approach that led to the co-design of a prospective observational study investigating the lived experience of adolescents with the rare disease, X-linked hypophosphataemia. Specifically, we describe how the knowledge and expertise of a diverse research team, which included expert physicians, research and technology specialists, patients and caregivers, were applied in order to identify the relevant research questions and to ensure the robustness of the study design and its appropriateness to the population of interest within the context of the current clinical landscape. We also demonstrate how a structured patient engagement exercise was key to informing the selection of appropriate outcome measures, data sources, timing of data collection, and to assessing the feasibility and acceptability of the proposed data collection approach.

Automation is an important element in modern livestock farming. Image computer analysis is the automation technology aiming to monitor farm animals by recording continuous images. Further analysis can be carried out to assess more precisely and effectively farm animals’ welfare. The aim of this study was to determine the applicability of the commercial multi-sensor device (Peek Analytics) developed by Copeeks SAS (France), in comparison to human-based observations used to assess behaviors in pigs, including posture (standing/resting), area within the pen (feeding/drinking/resting/enrichment), and activity level (number of active pigs). Two Peek Analytics (Peek 3 and Peek 4) were installed on a commercial fattening pig farm in Murcia (Spain). Each device recorded data of two pens (39 pigs in four pens in total). Scan sampling was the human-based behavioral observation method used in this study. Data was collected for five consecutive days, in the following intervals: 09:00-11:00, 13:00-15:00, and 16:00-18:00 (30 hours of observation in total). Every pig was observed six times per hour and hence the information analyzed includes 7020 observations (180 observations/pig). The comparison between data from human observation and Peek Analytics was performed by using Pearson correlation tests. Posture, areas of interest, and activity level were analyzed separately, as well as data recorded by Peek 3 and 4. Results indicated that Peek Analytics showed a better agreement with human observation, when recording posture(r=0.77, P

RESUMEN El objetivo de este estudio es describir la incidencia de bullying LGBTfóbico y analizar los factores que pueden influir en el clima escolar entre los adolescentes LGBT+. Un total de 164 adolescentes LGBT+ de 12 a 18 años respondieron una encuesta centrada en conocer sus percepciones sobre el bullying LGBTfóbico. El análisis evidenció que existen factores de protección que favorecen la disminución de la incidencia de bullying LGBTfóbico. Pese a ello, parte de la muestra ha reportado acoso escolar, lo que indica a la necesidad de análisis de dichas acciones. Se considera urgente que los centros educativos velen por la seguridad del alumnado. Ese contexto puede ser uno de los mejores canales de intervención para provocar el cambio social positivo hacia la igualdad.

Summary: Here, we present a protocol to study and describe immune cells that surround or infiltrate tumor cells or get through the body of a melanoma syngeneic mice model. We describe steps for creating and establishing the syngeneic mouse model, euthanasia, and tumor or organ harvest. We then detail procedures to rapidly achieve a single-cell suspension from different tissue samples to further quantify and analyze the phenotype of the immune cell population (lymphocytes T and B, tumor-associated macrophages, and myeloid-derived suppressor cells) by flow cytometry. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In the context of pig farming, this paper addresses the optimization problem of collecting fattened pigs from farms to deliver them to the abattoir. Assuming that the pig sector is organized as a competitive supply chain with narrow profit margins, our aim is to apply analytics to cope with the uncertainty in production costs and revenues. Motivated by a real-life case, the paper analyzes a rich Team Orienteering Problem (TOP) with a homogeneous fleet, stochastic demands, and maximum workload. After describing the problem and reviewing the related literature, we introduce the PJS heuristic. Our approach is first compared with exact methods, which are revealed as computationally unfeasible. Later, a scenario analysis based on a real instance was performed to gain insight into the practical aspects. Our findings demonstrate a positive correlation between the number of alternative routes explored, the number of trips, the transportation cost, and the maximum reward. Regarding the variability in the number of pigs to collect, when a truck can visit more than one farm, better solutions can be found with higher variability since the load can be combined more efficiently.

Developmental dyslexia and attention-deficit/hyperactivity disorder (ADHD) co-occur in 15–40% of individuals diagnosed with one disorder. Despite substantial research on the cognitive profiles of preschoolers at risk for either dyslexia or ADHD, studies have neglected children at risk for co-occurring dyslexia and ADHD. Thus, our study compared the cognitive profile of preschoolers at risk for dyslexia with the profile of children at risk for co-occurring dyslexia and ADHD. We assessed 50 preschoolers at dyslexia risk (DR), 50 at dyslexia + ADHD risk (DAR), and 48 without risk (NR) (Mage = 67 months). Our assessment encompassed phonological processing, executive functioning (EF), receptive vocabulary, and processing speed. Principal component analysis revealed two distinct components within the measures of EF, a verbal short-term memory and an EF component. ANOVA revealed that the NR group outperformed risk groups across measures, except for cognitive flexibility and delay of gratification. Notably, the DR and DAR groups did not differ in most measures but showed near-significant differences on the EF component, with the DR group having higher composite scores than the DAR group. In conclusion, ADHD risk did not impact the cognitive performance of children at risk for dyslexia but might amplify EF problems that at-risk preschoolers encounter.

The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPPβ, Aβ40, Aβ42, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM (p = 0.04) and HFMSE (p = 0.05) at 24 months. A reduction in sAPPβ levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, Aβ40, and Aβ42) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings.

The use of non-invasive liquid biopsy-based cell-free DNA (cfDNA) analysis is an emerging method of cancer detection and intervention. Different analytical methodologies are used to investigate cfDNA characteristics, resulting in costly and long analysis processes needed for combining different data. This study investigates the possibility of using cfDNA data converted for methylation analysis for combining the cfDNA fragment size with copy number variation (CNV) in the context of early colorectal cancer detection. Specifically, we focused on comparing enzymatically and bisulfite-converted data for evaluating cfDNA fragments belonging to chromosome 18. Chromosome 18 is often reported to be deleted in colorectal cancer. We used counts of short and medium cfDNA fragments of chromosome 18 and trained a linear model (LDA) on a set of 2959 regions to predict early-stage (I–IIA) colorectal cancer on an independent test set. In total, 87.5% sensitivity and 92% specificity were obtained on the enzymatically converted libraries. Repeating the same workflow on bisulfite-converted data yielded lower accuracy results with 58.3% sensitivity, implying that enzymatic conversion preserves the cancer fragmentation footprint in whole genome data better than bisulfite conversion. These results could serve as a promising new avenue for the early detection of colorectal cancer using fragmentation and methylation approaches on the same datasets.

Abstract Extracellular vesicles (EVs) play a crucial role in intercellular communication, participating in the paracrine trophic support or in the propagation of toxic molecules, including proteins. RTP801 is a stress‐regulated protein, whose levels are elevated during neurodegeneration and induce neuron death. However, whether RTP801 toxicity is transferred trans‐neuronally via EVs remains unknown. Hence, we overexpressed or silenced RTP801 protein in cultured cortical neurons, isolated their derived EVs (RTP801‐EVs or shRTP801‐EVs, respectively), and characterized EVs protein content by mass spectrometry (MS). RTP801‐EVs toxicity was assessed by treating cultured neurons with these EVs and quantifying apoptotic neuron death and branching. We also tested shRTP801‐EVs functionality in the pathologic in vitro model of 6‐Hydroxydopamine (6‐OHDA). Expression of RTP801 increased the number of EVs released by neurons. Moreover, RTP801 led to a distinct proteomic signature of neuron‐derived EVs, containing more pro‐apoptotic markers. Hence, we observed that RTP801‐induced toxicity was transferred to neurons via EVs, activating apoptosis and impairing neuron morphology complexity. In contrast, shRTP801‐EVs were able to increase the arborization in recipient neurons. The 6‐OHDA neurotoxin elevated levels of RTP801 in EVs, and 6‐OHDA‐derived EVs lost the mTOR/Akt signalling activation via Akt and RPS6 downstream effectors. Interestingly, EVs derived from neurons where RTP801 was silenced prior to exposing them to 6‐OHDA maintained Akt and RPS6 transactivation in recipient neurons. Taken together, these results suggest that RTP801‐induced toxicity is transferred via EVs, and therefore, it could contribute to the progression of neurodegenerative diseases, in which RTP801 is involved.

Total element concentrations by themselves are not always good predictors of toxicity and are therefore not suitable for eco- and/or human toxicological risk determination. In addition, despite the growing call for harmonization, countries show significant variation in risk assessment tools, screening/background values, protocols and legal management of soils. By incorporating mobility and bioaccessibility/availability into soil risk assessments, location-specific physico-chemical and geological conditions can be considered in routinely applied general risk assessment methodologies. Minette soils and rocks are a great case in point since they often are associated with high geogenic As concentrations and consequently potential risks. Minette iron ores form the world largest Fe ore deposits since the “great oxidation”. For the first time, oral bioaccessibility during direct ingestion was assessed on Minettes from Luxembourg by applying the in vitro Solubility/Bioavailability Research Consortium (SBRC) method. Out of > 180 samples, 25 representative samples were selected providing a unique dataset which showed an average gastric bioaccessibility of ∼10% (7.8 ± 4.0 mg/kg) of the total As-concentration, with a maximum of 45% (17.9 mg/kg). Of importance is that bioaccessibility of As in Minette rocks and soils are controlled by, and can be estimated from, lithology, mineralogy and total Ca content. Soils and ooid grainstones with an iron oxide or clayey matrix, are characterized by average gastric bioaccessible As concentrations

Background Using reports of randomised trials of smoking cessation interventions as a test case, this study aimed to develop and evaluate machine learning (ML) algorithms for extracting information from study reports and predicting outcomes as part of the Human Behaviour-Change Project. It is the first of two linked papers, with the second paper reporting on further development of a prediction system. Methods Researchers manually annotated 70 items of information (‘entities’) in 512 reports of randomised trials of smoking cessation interventions covering intervention content and delivery, population, setting, outcome and study methodology using the Behaviour Change Intervention Ontology. These entities were used to train ML algorithms to extract the information automatically. The information extraction ML algorithm involved a named-entity recognition system using the ‘FLAIR’ framework. The manually annotated intervention, population, setting and study entities were used to develop a deep-learning algorithm using multiple layers of long-short-term-memory (LSTM) components to predict smoking cessation outcomes. Results The F1 evaluation score, derived from the false positive and false negative rates (range 0-1), for the information extraction algorithm averaged 0.42 across different types of entity (SD=0.22, range 0.05-0.88) compared with an average human annotator’s score of 0.75 (SD=0.15, range 0.38-1.00). The algorithm for assigning entities to study arms (e.g., intervention or control) was not successful. This initial ML outcome prediction algorithm did not outperform prediction based just on the mean outcome value or a linear regression model. Conclusions While some success was achieved in using ML to extract information from reports of randomised trials of smoking cessation interventions, we identified major challenges that could be addressed by greater standardisation in the way that studies are reported. Outcome prediction from smoking cessation studies may benefit from development of novel algorithms, e.g., using ontological information to inform ML (as reported in the linked paper (1)).