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H pilin cyclisation and pilus biogenesis are promiscuous but electrostatic perturbations impair conjugation efficiency
No full textDuring conjugation, plasmid DNA is transferred from donor to recipient bacteria via the plasmid-encoded mating pilus, formed as thin helical assemblies of polymerised pilin subunits. In the IncHI1 R27 plasmid-encoded pilus, the TrhA pilin undergoes cyclisation (via a peptide bond between Gly1 and Asp69), essential for conjugation. Gly1 and Asp69 are exposed on the pilus surface and conserved in all TrhA pilins in the Plascad database. Substituting Asp69 with Asn, Ala, Gly, or Arg does not prevent cyclisation or pilus formation, which remains structurally indistinguishable from the wild type. Conjugation efficiency of the Asp69 substitutions across multiple recipient species correlates with side chain size, in the order Asp69Asn > Asp69Ala > Asp69Gly. However, Asp69Arg, as well as Asp69Lys and Gly1Lys substitutions abolish conjugation, likely due to the positively charged pilus surface (opposite to the wild-type negative charge) forming unfavourable electrostatic interactions with the recipient outer membrane’s inner leaflet, composed solely of zwitterionic phosphatidylethanolamine (PE). Consistently, conjugation is rescued in recipients lacking PE. These findings indicate strong selective pressure to maintain Gly1 and Asp69, as efficient DNA transfer depends on precise electrostatic and steric constraints of the pilus surface
Automated opportunistic cardiovascular risk assessment in non-small cell lung cancer patients on routine chest CT using an optimised nnU-net framework
No full textBackground: Cardiovascular disease (CVD) and non-small cell lung cancer (NSCLC) are the global leading causes of overall and cancer-related deaths, respectively. NSCLC patients have a higher CVD risk than the general population which is frequently underdiagnosed. Coronary artery calcification (CAC), a marker of CVD, is commonly detected on routinely acquired CT from NSCLC work-up but often not reported. We present an automated CAC assessment tool validated for NSCLC patients using a deep learning-based framework to provide valuable, non-invasive CVD screening opportunity without incurring extra workload or radiation exposure.
Methods: We trained nnU-Net models on ungated, unenhanced chest CTs (n=97) from Stanford AIMI dataset, and tested them on three mutually independent datasets: (1) ungated unenhanced CTs from AIMI (n=95), (2) attenuation correction CTs from PET-CT scans of NSCLC patients at our institution (ICHNT, n=87; age 67.8±10.1 years; M:F 174:113), and (3) CAC-negative scans from TCIA (n=50). The best model produced CAC segmentations, post-processed with TotalSegmentator, to stratify patients into CVD risk groups, informing the need for dedicated cardiac clinic assessment.
Results: For a CAC threshold of 100, the model achieved accuracy: 83.6%, sensitivity: 91.9%, specificity: 70.8%, positive predictive value (PPV): 82.9%, negative predictive value (NPV): 85.1%, F1-score: 0.87, and kappa coefficient: 0.65. For a threshold of 400, accuracy: 84.5%, sensitivity: 90.9%, specificity: 79.5%, PPV: 77.6%, NPV: 91.8%, F1-score: 0.84, and kappa coefficient: 0.69.
Conclusion: Our optimised deep learning model can provide value to NSCLC patients in the form of free additional information which may not acted upon otherwise, thus enabling a practical CVD risk opportunistic screening solution for its patients
Three-dimensional effects on carbon capture in wavy falling films
No full textWave evolution in thin-film flows is highly relevant for heat and mass transfer applications, such as CO2
capture
in falling film absorbers. To develop a detailed understanding of potential enhancement mechanisms associated
with the evolution of three-dimensional (3D) waveforms, we perform 3D direct numerical simulations
of passive scalar transport in laminar-wavy film flows, using a hybrid front-tracking/level-set method to
accurately resolve interfacial features. CO2 absorption is greatly enhanced in the presence of interfacial waves
with the liquid-side mass transfer coefficient increasing tenfold relative to that of a flat film for the highest
film Reynolds numbers () studied. This is primarily due to changes in interfacial and internal flow dynamics
rather than an increase in the gas-liquid interfacial area. The recirculation region present in the leading and
trailing fronts of the 3D waves intensifies mass transfer, and their effectiveness increases with . At low ,
there is a film region beneath the wavy interface, which remains relatively undisturbed where mass transfer
is dominated by diffusion. The introduction of structured substrates to promote mass transfer under these
conditions is recommended. The visco-capillary ripple region, which precedes the leading and trailing fronts for sufficiently high , provides a relatively high degree of spanwise advection, with the mean spanwise velocity
magnitude reaching around one-quarter that in the streamwise direction. This underscores the importance of solving the fully-3D problem as these effects do not have a two-dimensional analogue
UK land use implications of replacing dairy farming with precision fermentation
No full textReducing animal agriculture is key to releasing land needed to achieve global environmental goals. Precision fermentation (PF) is a technology using genetically engineered microbes to produce ingredients such as dairy proteins. Few studies have quantified PF’s land-sparing potential. Using the UK as a case study, we assess the land use implications of scaling up the production of PF milk (plant-based milk containing PF dairy protein), by calculating and summing land footprints (area/mass) of PF milk’s individual components. PF milk’s land footprint was estimated to be as much as 96% lower than that of cow’s milk. Replacing 20%, 50% or 100% of UK-produced cow’s milk with PF milk was estimated to release 859kha, 2,147kha or 4,294kha of land by 2050. This corresponds to 40-202% of required permanent grassland and 16-82% of required cropland to meet the UK Climate Change Committee’s 2050 ‘Balanced Net Zero’ targets regarding afforestation, bioenergy, peatland restoration (lowland grassland only), agroforestry and hedgerow creation. These results suggest PF could play a critical role in releasing land for Net Zero measures and alleviating land use pressures in the UK and globally. Further research is required to address knowledge gaps and facilitate more nuanced assessments of PF’s land-sparing potential
Medical image upsampling algorithm to reduce errors in grid-based ultrasound simulation
No full textClinical imaging resolution is often insufficient for accurate ultrasound simulation in personalised treatment planning. Naive image upsampling algorithms introduce artifacts that reduce simulation accuracy. We develop a Gaussian smoothing and mesh-based upsampling method and evaluate upsampled image fidelity and ultrasound simulation accuracy using an ex vivo high resolution human cervical vertebra volume obtained with hierarchical phase-contrast tomography, against linear and nearest
neighbour interpolation. The mesh-based method significantly and consistently reduced L2 and L∞ errors, and reduced focal errors with inconsistent significance. Medical image upsampling for ultrasound simulation should be completed with edge-aware
methods to improve accuracy
A tiger is not always a satyr: role of male mating behaviour in interspecific mating interactions between Aedes aegypti and Aedes albopictus
No full textBackground: Interspecific mating between Aedes aegypti and Aedes albopictus, which act as vectors of a wide range of arboviruses, is predicted to have an important influence on their future distributions and disease control efforts. While interspecific insemination has been documented in a range of laboratory and field studies, rates vary between populations. It has
been suggested that the outcome of mating interactions is driven by evolved variation in both the male ability to mate interspecific females and ability of females to resist interspecific males. However, there has been relatively little dissection of the behaviours that underlie interspecific insemination rates.
Methods: We compared insemination rates between sympatric, allopatric, and lab-adapted strains of Ae. aegypti (Colombia, Arizona, and Liverpool, respectively) and allopatric and sympatric strains of Ae. albopictus (Montpellier and Colombia, respectively). We then used
both live observations and high-speed videography to compare intraspecific and interspecific mating interactions.
Results: We found very low rates of interspecific mating across all strains used. Both behavioural observations and high-speed videography suggested that female resistance behaviours were not responsible for low interspecific mating. Interestingly, we documented male Ae. albopictus consistently aborting interspecific mating attempts.
Conclusions: This study provides additional evidence for strong pre-copulatory species barriers between Ae. aegypti and Ae. albopictus species and adds male avoidance as a possible mechanism to maintain these barriers. Considering female resistance, the ability of males to overcome that resistance, and male avoidance of interspecific matings together will be important for informing understanding of how we expect interspecific mating rates to vary across populations and respond to selective pressures such as mass-release strategies
Impacts of liver resection with neoadjuvant treatment versus surgery alone in hepatocellular carcinoma with portal vein tumour thrombosis: a systematic review and meta-analysis
No full textBackground/Objectives: Hepatocellular carcinoma (HCC) with Portal Vein Tumour Thrombosis (PVTT) is an advanced-stage (BCLC-C) disease, typically managed with systemic therapy. While surgical resection is increasingly offered, the role of neoadjuvant
treatments (NAT) remains unquantified. This systematic review and meta-analysis evaluate the impact of NAT followed by surgery versus surgery alone on survival outcomes for patients with HCC with PVTT. Methods: A PRISMA-compliant systematic review was conducted by searching OVID- Embase, Medline, PubMed, and Scopus databases up to January 23, 2025. Two independent authors screened articles. Risks of bias were assessed using the ROBINS-I tool for non-randomised studies and the Cochrane risk of bias (ROB-
2) tool for randomised controlled trials. The methodological quality was evaluated using
the Newcastle–Ottawa Scale (NOS). Hazard ratios (HRs) for overall survival (OS) and Recurrence-free survival (RFS) were pooled for meta-analysis. Results: Seven studies met the inclusion criteria. The pooled analysis demonstrated that NAT followed by surgery was associated with a significantly improved overall survival (HR: 0.48, 95% CI: 0.295-0.67, p-value <0.001, I2 = 0.00) and improved recurrence-free survival (RFS) (HR: 0.4, 95% CI: 0.2-0.58, p-value <0.001, I2 = 0.00) compared to direct-to-surgery. Conclusions: For patients with HCC and an associated PVTT, neoadjuvant treatment before surgery significantly improves both overall and recurrence-free survival. These findings support a multimodal approach. Future multicenter randomised controlled trials may be needed to identify optimal NAT strategies in this patient population
Understanding ischemia in children with tuberculous meningitis (iThemba): a protocol paper
No full textBackground
One million children develop tuberculosis (TB) each year and a quarter of these die. TB meningitis (TBM) is the most severe form of TB disease and even if diagnosed and treated, 20% die and over 50% of survivors are left with permanent neurological disability. Much of the morbidity and mortality associated with TBM is due to infarction yet, despite this, our understanding of the pathogenesis of infarction in TBM remains limited, especially in children.
Methods
The iThemba study (Understanding ischemia in children with tuberculous meningitis), aims to recruit 100 children with probable or confirmed TBM and obtain samples of blood and cerebrospinal fluid (CSF). All children will undergo MRI and FDG PET/CT at baseline and will have repeat MRI with further blood and CSF samples collected at 2 weeks’ follow-up. MRI will then be carried out at 24 weeks with neurodevelopmental assessment at 48 weeks. Neuroimaging will focus on methods to identify and characterize ischemic penumbra and evaluate how this correlates with clinical outcomes. RNA sequencing of blood and CSF will be used to identify differentially expressed genes and identify implicated biological pathways between children with and without infarction. Targeted proteomic profiling will be performed on plasma and CSF to determine differences in protein abundance, with a focus on proteins involved in coagulation and endothelial function. Finally, we will integrate transcriptomic, proteomic and radiomic data to generate a comprehensive understanding of the pathogenesis of infarction in children with TBM. We aim to group children into relevant biological/anatomical phenotypes, each of which may benefit from a different therapeutic approach. Using computer simulation, we will then explore the impact of potential therapeutic interventions on biological pathways for each distinct phenotype. This work may pave the way for the development of point-of-care tests at diagnosis that could allow for stratified novel therapeutic approaches in future.
Discussion
A more comprehensive understanding of the pathophysiology of infarction in children with TBM would permit targeted host-directed therapies, with the potential to moderate or eliminate the consequences of this devastating condition
Porphyrin-nitrogen carbon dot composites for high-performance organic light-emitting diodes
No full textFluorescent organic light-emitting diodes (OLEDs) still face major obstacles to combining high efficiency with solution processability and energy-sustainable operation. In this work, a tetra-carboxyphenyl porphyrin–nitrogen carbon dots (TCPP-NCDots) derivative is introduced as a solution-processable electron transport layer (ETL) in OLEDs based on a green–yellow emissive polymer. The structural, optical, and electronic properties of the TCPP-NCDots ETL are comprehensively characterised by ultraviolet–visible absorption spectroscopy, steady-state photoluminescence, Fourier-transform infrared spectroscopy, atomic force microscopy, and cyclic voltammetry. These studies reveal a synergistic effect of porphyrin functionalisation on the carbon dots, which improves electron injection and transport toward the emissive layer. At an optimum concentration of 1 mg mL−1, the TCPP-NCDots ETL yields a 21.6% enhancement in external quantum efficiency compared with the reference device without an ETL, while simultaneously suppressing efficiency roll-off. The optimised devices also maintain stable operation under ambient conditions, highlighting TCPP-NCDots as a promising, sustainable ETL platform for next-generation fluorescent OLEDs
Post-pandemic vaccination adherence in patients with Inflammatory Bowel Disease: a cross-sectional observational study
No full textObjective: Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy are at increased infection risk. Although many infections are vaccine-preventable, uptake in IBD remains suboptimal, and hesitancy has increased since the COVID-19 pandemic. We assessed adherence to vaccination recommendations and barriers to uptake among immunosuppressed IBD patients in North West London.
Methods: A paper-based survey was completed by 209 IBD patients attending St Mark’s Hospital and Imperial College Healthcare NHS Trust between 19 February and 19 April 2024. Data on demographics, vaccination history, and prior counselling were collected. The primary composite outcome was receipt of pneumococcal, influenza, and SARS-CoV-2 vaccines within recommended timeframes, according to UK guidelines for immunosuppressed patients. Univariate and multivariate analyses identified factors associated with uptake, and adherence to national guidance on pre-treatment vaccine counselling was evaluated.
Results: Of 194 patients on immunosuppressive medication, only 22.2% were fully vaccinated. Uptake remained low for pneumococcal (30.9%), COVID-19 booster (56.7%), and influenza (64.4%) vaccines. Older age and receiving vaccine recommendations from healthcare professionals were significantly associated with uptake (OR 1.03 (1.00–1.07) and OR 3.43 (1.73–6.92), respectively). Common barriers included uncertainty about necessity, limited awareness, and safety concerns. Over 40% reported inadequate counselling before starting immunosuppression. Vaccine recommendations from healthcare professionals were infrequent (66.8% for influenza, 59.1% for COVID-19 booster, 22.4% for Shingrix®).
Conclusion: Vaccination uptake among immunosuppressed IBD patients remains low in the post-pandemic era. Clinicians and the wider multidisciplinary team should actively promote vaccination, given the strong association between healthcare professional-led counselling and improved uptake