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Open Access
Eggshell composition and surface properties of avian brood-parasitic species compared with non-parasitic species.
(2023-05-24) McClelland, Stephanie C; Attard, Marie R G; Bowen, James; Horrocks, Nicholas P C; Jamie, Gabriel A; Dixit, Tanmay; Spottiswoode, Claire N; Portugal, Steven J; McClelland, Stephanie C [0000-0002-8763-2291]; Attard, Marie R G [0000-0002-8509-3677]; Horrocks, Nicholas P C [0000-0003-0762-4142]; Jamie, Gabriel A [0000-0002-2766-7687]; Dixit, Tanmay [0000-0001-5604-7965]; Portugal, Steven J [0000-0002-2438-2352]
The eggs of avian obligate brood-parasitic species have multiple adaptations to deceive hosts and optimize development in host nests. While the structure and composition of the eggshell in all birds is essential for embryo growth and protection from external threats, parasitic eggs may face specific challenges such as high microbial loads, rapid laying and ejection by the host parents. We set out to assess whether eggshells of avian brood-parasitic species have either (i) specialized structural properties, to meet the demands of a brood-parasitic strategy or (ii) similar structural properties to eggs of their hosts, due to the similar nest environment. We measured the surface topography (roughness), wettability (how well surfaces repel water) and calcium content of eggshells of a phylogenetically and geographically diverse range of brood-parasitic species (representing four of the seven independent lineages of avian brood-parasitic species), their hosts and close relatives of the parasites. These components of the eggshell structure have been demonstrated previously to influence such factors as the risk of microbial infection and overall shell strength. Within a phylogenetically controlled framework, we found no overall significant differences in eggshell roughness, wettability and calcium content between (i) parasitic and non-parasitic species, or (ii) parasitic species and their hosts. Both the wettability and calcium content of the eggs from brood-parasitic species were not more similar to those of their hosts' eggs than expected by chance. By contrast, the mean surface roughness of the eggs of brood-parasitic species was more similar to that of their hosts' eggs than expected by chance, suggesting brood-parasitic species may have evolved to lay eggs that match the host nest environment for this trait. The lack of significant overall differences between parasitic and non-parasitic species, including hosts, in the traits we measured, suggests that phylogenetic signal, as well as general adaptations to the nest environment and for embryo development, outweigh any influence of a parasitic lifestyle on these eggshell properties.
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Open Access
Human Archaeological Dentin as Source of Polar and Less Polar Metabolites for Untargeted Metabolomic Research: The Case of Yersinia pestis.
(2023-04-24) Badillo-Sanchez, Diego Armando; Jones, Donald J L; Inskip, Sarah A; Scheib, Christiana L; Badillo-Sanchez, Diego Armando [0000-0002-0588-690X]; Jones, Donald J L [0000-0001-6583-870X]; Inskip, Sarah A [0000-0001-7424-2094]; Scheib, Christiana L [0000-0003-4158-8296]
Metabolomic approaches, such as in clinical applications of living individuals, have shown potential use for solving questions regarding the past when applied to archaeological material. Here, we study for the first time the potential of this Omic approach as applied to metabolites extracted from archaeological human dentin. Dentin obtained from micro sampling the dental pulp of teeth of victims and non-victims of Yersinia pestis (plague) from a 6th century Cambridgeshire site are used to evaluate the potential use of such unique material for untargeted metabolomic studies on disease state through liquid chromatography hyphenated to high-resolution mass spectrometry (LC-HRMS). Results show that small molecules of both likely endogenous and exogenous sources are preserved for a range of polar and less polar/apolar metabolites in archaeological dentin; however, untargeted metabolomic profiles show no clear differentiation between healthy and infected individuals in the small sample analysed (n = 20). This study discusses the potential of dentin as a source of small molecules for metabolomic assays and highlights: (1) the need for follow up research to optimise sampling protocols, (2) the requirements of studies with larger sample numbers and (3) the necessity of more databases to amplify the positive results achievable with this Omic technique in the archaeological sciences.
Open Access
Extraction and generalisation of category-level information during visual statistical learning in autistic people
(Public Library of Science, 2023-06-02) Parsons, Owen; Baron-Cohen, Simon; Parsons, Owen [0000-0003-0163-5609]
Background: We examined whether information extracted during a visual statistical learning task could be generalised from specific exemplars to semantically similar ones. We then looked at whether performance in autistic people differed to non-autistic people during a visual statistical learning task and specifically examined whether differences in performance between groups occurred when sequential information was presented at a semantic level. We did this by assessing recall performance using a two-alternative forced choice paradigm after presenting participants with a sequence of naturalistic scene images. Methods: 125 adult participants (61 participants with an autism diagnosis and 64 non-autistic controls) were presented with a fast serial presentation sequence of images and given a cover task to avoid attention being explicitly drawn to patterns in the underlying sequences. This was followed by a two-alternative forced choice task to assess participants’ implicit recall. Participants were presented with 1 of 3 unique versions of the task, in which the presentation and assessment of statistical regularities was done at either a low feature-based level or a high semantic-based level. Results: Participants were able to generalise statistical information from specific exemplars to semantically similar ones. There was an overall significant reduction in visual statistical learning in the autistic group but we were unable to determine whether group differences occurred specifically in conditions where the learning of semantic information was required. Conclusions: These results provide evidence that participants are able to extract statistical information that is presented at the level of specific exemplars and generalise it to semantically similar contexts. We also showed a modest but statistically significant reduction in recall performance in the autistic participants relative to the non-autistic participants.
Open Access
Daughter centrioles assemble preferentially towards the nuclear envelope in Drosophila syncytial embryos
(The Royal Society, 2022-01-19) Cunningham, Neil H. J.; Bouhlel, Imène B.; Conduit, Paul T.; Bouhlel, Imène B. [0000-0001-5876-4597]; Conduit, Paul T. [0000-0002-7822-1191]
Centrosomes are important organizers of microtubules within animal cells. They comprise a pair of centrioles surrounded by the pericentriolar material, which nucleates and organizes the microtubules. To maintain centrosome numbers, centrioles must duplicate once and only once per cell cycle. During S-phase, a single new ‘daughter’ centriole is built orthogonally on one side of each radially symmetric ‘mother’ centriole. Mis-regulation of duplication can result in the simultaneous formation of multiple daughter centrioles around a single mother centriole, leading to centrosome amplification, a hallmark of cancer. It remains unclear how a single duplication site is established. It also remains unknown whether this site is pre-defined or randomly positioned around the mother centriole. Here, we show that within Drosophila syncytial embryos daughter centrioles preferentially assemble on the side of the mother facing the nuclear envelope, to which the centrosomes are closely attached. This positional preference is established early during duplication and remains stable throughout daughter centriole assembly, but is lost in centrosomes forced to lose their connection to the nuclear envelope. This shows that non-centrosomal cues influence centriole duplication and raises the possibility that these external cues could help establish a single duplication site.
Open Access
Reflection and Timing Study of the Transient Black Hole X-Ray Binary MAXI J1803-298 with NuSTAR
(The American Astronomical Society, 2023-06-02) Coughenour, Benjamin M.; Tomsick, John A.; Mastroserio, Guglielmo; Steiner, James F.; Connors, Riley M. T.; Jiang, Jiachen; Hare, Jeremy; Shaw, Aarran W.; Ludlam, Renee M.; Fabian, A. C.; García, Javier A.; Coley, Joel B.; Coughenour, Benjamin M. [0000-0003-0870-6465]; Tomsick, John A. [0000-0001-5506-9855]; Mastroserio, Guglielmo [0000-0003-4216-7936]; Steiner, James F. [0000-0002-5872-6061]; Connors, Riley M. T. [0000-0002-8908-759X]; Jiang, Jiachen [0000-0002-9639-4352]; Hare, Jeremy [0000-0002-8548-482X]; Shaw, Aarran W. [0000-0002-8808-520X]; Ludlam, Renee M. [0000-0002-8961-939X]; Fabian, A. C. [0000-0002-9378-4072]; García, Javier A. [0000-0003-3828-2448]; Coley, Joel B. [0000-0001-7532-8359]
The transient black hole X-ray binary MAXI J1803−298 was discovered on 2021 May 1, as it went into outburst from a quiescent state. As the source rose in flux it showed periodic absorption dips and fit the timing and spectral characteristics of a hard-state accreting black hole. We report on the results of a Target-of-Opportunity observation with NuSTAR obtained near the peak outburst flux beginning on 2021 May 13, after the source had transitioned into an intermediate state. MAXI J1803−298 is variable across the observation, which we investigate by extracting spectral and timing products separately for different levels of flux throughout the observation. Our timing analysis reveals two distinct potential quasiperiodic oscillations (QPOs) which are not harmonically related at 5.4 ± 0.2 Hz and 9.4 ± 0.3 Hz, present only during periods of lower flux. With clear relativistic reflection signatures detected in the source spectrum, we applied several different reflection models to the spectra of MAXI J1803−298. Here we report our results, utilizing high-density reflection models to constrain the disk geometry, and assess changes in the spectrum dependent on the source flux. With a standard broken power-law emissivity, we find a near-maximal spin for the black hole, and we are able to constrain the inclination of the accretion disk at 75° ± 2°, which is expected for a source that has shown periodic absorption dips. We also significantly detect a narrow absorption feature at 6.91 ± 0.06 keV with an equivalent width between 4 and 9 eV, which we interpret as the signature of a disk wind.
Open Access
Particular genomic and virulence traits associated with preterm infant-derived toxigenic Clostridium perfringens strains.
(Springer Science and Business Media LLC, 2023-05-25) Kiu, Raymond; Shaw, Alexander G; Sim, Kathleen; Acuna-Gonzalez, Antia; Price, Christopher A; Bedwell, Harley; Dreger, Sally A; Fowler, Wesley J; Cornwell, Emma; Pickard, Derek; Belteki, Gusztav; Malsom, Jennifer; Phillips, Sarah; Young, Gregory R; Schofield, Zoe; Alcon-Giner, Cristina; Berrington, Janet E; Stewart, Christopher J; Dougan, Gordon; Clarke, Paul; Douce, Gillian; Robinson, Stephen D; Kroll, J Simon; Hall, Lindsay J; Kiu, Raymond [0000-0002-4483-1215]; Acuna-Gonzalez, Antia [0000-0002-8062-925X]; Price, Christopher A [0000-0003-3161-1704]; Dreger, Sally A [0000-0001-7104-6776]; Young, Gregory R [0000-0001-5342-1421]; Stewart, Christopher J [0000-0002-6033-338X]; Clarke, Paul [0000-0001-6203-7632]; Douce, Gillian [0000-0002-6654-7346]; Robinson, Stephen D [0000-0002-6606-7588]; Hall, Lindsay J [0000-0001-8938-5709]
Clostridium perfringens is an anaerobic toxin-producing bacterium associated with intestinal diseases, particularly in neonatal humans and animals. Infant gut microbiome studies have recently indicated a link between C. perfringens and the preterm infant disease necrotizing enterocolitis (NEC), with specific NEC cases associated with overabundant C. perfringens termed C. perfringens-associated NEC (CPA-NEC). In the present study, we carried out whole-genome sequencing of 272 C. perfringens isolates from 70 infants across 5 hospitals in the United Kingdom. In this retrospective analysis, we performed in-depth genomic analyses (virulence profiling, strain tracking and plasmid analysis) and experimentally characterized pathogenic traits of 31 strains, including 4 from CPA-NEC patients. We found that the gene encoding toxin perfringolysin O, pfoA, was largely deficient in a human-derived hypovirulent lineage, as well as certain colonization factors, in contrast to typical pfoA-encoding virulent lineages. We determined that infant-associated pfoA+ strains caused significantly more cellular damage than pfoA- strains in vitro, and further confirmed this virulence trait in vivo using an oral-challenge C57BL/6 murine model. These findings suggest both the importance of pfoA+ C. perfringens as a gut pathogen in preterm infants and areas for further investigation, including potential intervention and therapeutic strategies.
Open Access
Human soluble CD39 displays substrate inhibition in a substrate-specific manner
(Nature Publishing Group UK, 2023-06-02) Vadlamani, Venkat M. K.; Gunasinghe, Kavinda K. J.; Chee, Xavier W.; Rahman, Taufiq; Harper, Matthew T.
CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD1) metabolizes extracellular ATP and ADP to AMP. AMP is subsequently metabolized by CD79 to adenosine. CD39 activity is therefore a key regulator of purinergic signalling in cancer, thrombosis, and autoimmune diseases. In this study we demonstrate that soluble, recombinant CD39 shows substrate inhibition with ADP or ATP as the substrate. Although CD39 activity initially increased with increasing substrate concentration, at high concentrations of ATP or ADP, CD39 activity was markedly reduced. Although the reaction product, AMP, inhibits CD39 activity, insufficient AMP was generated under our conditions to account for the substrate inhibition seen. In contrast, inhibition was not seen with UDP or UTP as substrates. 2-methylthio-ADP also showed no substrate inhibition, indicating the nucleotide base is an important determinant of substrate inhibition. Molecular dynamics simulations revealed that ADP can undergo conformational rearrangements within the CD39 active site that were not seen with UDP or 2-methylthio-ADP. Appreciating the existence of substrate inhibition of CD39 will help the interpretation of studies of CD39 activity, including investigations into drugs that modulate CD39 activity.
Open Access
Merging bioactivity predictions from cell morphology and chemical fingerprint models using similarity to training data
(Springer International Publishing, 2023-06-02) Seal, Srijit; Yang, Hongbin; Trapotsi, Maria-Anna; Singh, Satvik; Carreras-Puigvert, Jordi; Spjuth, Ola; Bender, Andreas
The applicability domain of machine learning models trained on structural fingerprints for the prediction of biological endpoints is often limited by the lack of diversity of chemical space of the training data. In this work, we developed similarity-based merger models which combined the outputs of individual models trained on cell morphology (based on Cell Painting) and chemical structure (based on chemical fingerprints) and the structural and morphological similarities of the compounds in the test dataset to compounds in the training dataset. We applied these similarity-based merger models using logistic regression models on the predictions and similarities as features and predicted assay hit calls of 177 assays from ChEMBL, PubChem and the Broad Institute (where the required Cell Painting annotations were available). We found that the similarity-based merger models outperformed other models with an additional 20% assays (79 out of 177 assays) with an AUC > 0.70 compared with 65 out of 177 assays using structural models and 50 out of 177 assays using Cell Painting models. Our results demonstrated that similarity-based merger models combining structure and cell morphology models can more accurately predict a wide range of biological assay outcomes and further expanded the applicability domain by better extrapolating to new structural and morphology spaces. Graphical Abstract:
Open Access
Predictors of post-intubation hypotension in trauma patients following prehospital emergency anaesthesia: a multi-centre observational study
(BioMed Central, 2023-06-02) Price, James; Moncur, Lyle; Lachowycz, Kate; Major, Rob; Sagi, Liam; McLachlan, Sarah; Keeliher, Chris; Steel, Alistair; Sherren, Peter B.; Barnard, Ed B. G.; Price, James [0000-0002-9643-692X]
Background: Post-intubation hypotension (PIH) after prehospital emergency anaesthesia (PHEA) is prevalent and associated with increased mortality in trauma patients. The objective of this study was to compare the differential determinants of PIH in adult trauma patients undergoing PHEA. Methods: This multi-centre retrospective observational study was performed across three Helicopter Emergency Medical Services (HEMS) in the UK. Consecutive sampling of trauma patients who underwent PHEA using a fentanyl, ketamine, rocuronium drug regime were included, 2015–2020. Hypotension was defined as a new systolic blood pressure (SBP) < 90 mmHg within 10 min of induction, or > 10% reduction if SBP was < 90 mmHg before induction. A purposeful selection logistic regression model was used to determine pre-PHEA variables associated with PIH. Results: During the study period 21,848 patients were attended, and 1,583 trauma patients underwent PHEA. The final analysis included 998 patients. 218 (21.8%) patients had one or more episode(s) of hypotension ≤ 10 min of induction. Patients > 55 years old; pre-PHEA tachycardia; multi-system injuries; and intravenous crystalloid administration before arrival of the HEMS team were the variables significantly associated with PIH. Induction drug regimes in which fentanyl was omitted (0:1:1 and 0:0:1 (rocuronium-only)) were the determinants with the largest effect sizes associated with hypotension. Conclusion: The variables significantly associated with PIH only account for a small proportion of the observed outcome. Clinician gestalt and provider intuition is likely to be the strongest predictor of PIH, suggested by the choice of a reduced dose induction and/or the omission of fentanyl during the anaesthetic for patients perceived to be at highest risk.
Open Access
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration
(Springer Science and Business Media LLC, 2023-06-01) Koga, Shunsuke; Metrick, Michael A; Golbe, Lawrence I; Santambrogio, Alessia; Kim, Minji; Soto-Beasley, Alexandra I; Walton, Ronald L; Baker, Matthew C; De Castro, Cristhoper Fernandez; DeTure, Michael; Russell, David; Navia, Bradford A; Sandiego, Christine; Ross, Owen A; Vendruscolo, Michele; Caughey, Byron; Dickson, Dennis W; Koga, Shunsuke [0000-0001-8868-9700]
AbstractProgressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are distinct clinicopathological subtypes of frontotemporal lobar degeneration. They both have atypical parkinsonism, and they usually have distinct clinical features. The most common clinical presentation of PSP is Richardson syndrome, and the most common presentation of CBD is corticobasal syndrome. In this report, we describe a patient with a five-year history of Richardson syndrome and a family history of PSP in her mother and sister. A tau PET scan (18F-APN-1607) revealed low-to-moderate uptake in the substantia nigra, globus pallidus, thalamus and posterior cortical areas, including temporal, parietal and occipital cortices. Neuropathological evaluation revealed widespread neuronal and glial tau pathology in cortical and subcortical structures, including tufted astrocytes in the motor cortex, striatum and midbrain tegmentum. The subthalamic nucleus had mild-to-moderate neuronal loss with globose neurofibrillary tangles, consistent with PSP. On the other hand, there were also astrocytic plaques, a pathological hallmark of CBD, in the neocortex and striatum. To further characterize the mixed pathology, we applied two machine learning-based diagnostic pipelines. These models suggested diagnoses of PSP and CBD depending on the brain region – PSP in the motor cortex and superior frontal gyrus and CBD in caudate nucleus. Western blots of insoluble tau from motor cortex showed a banding pattern consistent with mixed features of PSP and CBD, whereas tau from the superior frontal gyrus showed a pattern consistent with CBD. Real-time quaking-induced conversion (RT-QuIC) using brain homogenates from the motor cortex and superior frontal gyrus showed ThT maxima consistent with PSP, while reaction kinetics were consistent with CBD. There were no pathogenic variants in MAPT with whole genome sequencing. We conclude that this patient had an unclassified tauopathy and features of both PSP and CBD. The different pathologies in specific brain regions suggests caution in diagnosis of tauopathies with limited sampling.
Open Access
Syndromes associated with frontotemporal lobar degeneration change response patterns on visual analogue scales
(Nature Publishing Group UK, 2023-06-02) Williams, Rebecca S.; Adams, Natalie E.; Hughes, Laura E.; Rouse, Matthew A.; Murley, Alexander G.; Naessens, Michelle; Street, Duncan; Holland, Negin; Rowe, James B.
Self-report scales are widely used in cognitive neuroscience and psychology. However, they rest on the central assumption that respondents engage meaningfully. We hypothesise that this assumption does not hold for many patients, especially those with syndromes associated with frontotemporal lobar degeneration. In this study we investigated differences in response patterns on a visual analogue scale between people with frontotemporal degeneration and controls. We found that people with syndromes associated with frontotemporal lobar degeneration respond with more invariance and less internal consistency than controls, with Bayes Factors = 15.2 and 14.5 respectively indicating strong evidence for a group difference. There was also evidence that patient responses feature lower entropy. These results have important implications for the interpretation of self-report data in clinical populations. Meta-response markers related to response patterns, rather than the values reported on individual items, may be an informative addition to future research and clinical practise.
Open Access
Bispalladium(II) Complexes of di‐ p ‐Pyrirubyrin Derivatives as Promising Near‐Infrared Photoacoustic Dyes
(2023-06-02) Hurej, Karolina; Oszczęda, Weronika; Opas, Ewelina; Zelewski, Szymon J.; Pawlicki, Miłosz; Białek, Michał J.; Orzeł, Łukasz; Latos‐Grażyński, Lechosław; Hurej, Karolina [0000-0002-5749-7658]; Zelewski, Szymon J. [0000-0002-6037-3701]; Pawlicki, Miłosz [0000-0002-8249-0474]; Białek, Michał J. [0000-0002-4890-2156]; Orzeł, Łukasz [0000-0002-6943-7441]; Latos‐Grażyński, Lechosław [0000-0003-1230-9075]
The insertion of palladium(II) into di‐p‐pyrirubyrin results in mutually convertible bimetallic complexes. Post‐synthetic functionalization of one of them yielded bispalladium(II) dioxo‐di‐p‐pyrirubyrin and, after demetallation, dioxo‐di‐p‐pyrirubyrin, introducing for the first time the α,β′‐pyridin‐2‐one unit into the macrocyclic frame. Bispalladium(II) di‐p‐pyrirubyrin 6, bispalladium(II) dioxo‐di‐p‐pyrirubyrin 9, and dioxo‐di‐p‐pyrirubyrin 10 absorb and emit light around 1000 nm and are characterized by high photostability. Thus, they are promising candidates for near‐infrared photoacoustic dyes, ideally targeting (9) the wavelength of Yb‐based fiber lasers. The incorporation of an α,β′‐pyridine moiety into expanded porphyrins opens a highly interesting area of research due to the attractive optical and coordination properties of the resulting molecules.
Open Access
Bispalladium(II) Complexes of di‐ p ‐Pyrirubyrin Derivatives as Promising Near‐Infrared Photoacoustic Dyes
(2023-06-02) Hurej, Karolina; Oszczęda, Weronika; Opas, Ewelina; Zelewski, Szymon J.; Pawlicki, Miłosz; Białek, Michał J.; Orzeł, Łukasz; Latos‐Grażyński, Lechosław; Hurej, Karolina [0000-0002-5749-7658]; Zelewski, Szymon J. [0000-0002-6037-3701]; Pawlicki, Miłosz [0000-0002-8249-0474]; Białek, Michał J. [0000-0002-4890-2156]; Orzeł, Łukasz [0000-0002-6943-7441]; Latos‐Grażyński, Lechosław [0000-0003-1230-9075]
The insertion of palladium(II) into di‐p‐pyrirubyrin results in mutually convertible bimetallic complexes. Post‐synthetic functionalization of one of them yielded bispalladium(II) dioxo‐di‐p‐pyrirubyrin and, after demetallation, dioxo‐di‐p‐pyrirubyrin, introducing for the first time the α,β′‐pyridin‐2‐one unit into the macrocyclic frame. Bispalladium(II) di‐p‐pyrirubyrin 6, bispalladium(II) dioxo‐di‐p‐pyrirubyrin 9, and dioxo‐di‐p‐pyrirubyrin 10 absorb and emit light around 1000 nm and are characterized by high photostability. Thus, they are promising candidates for near‐infrared photoacoustic dyes, ideally targeting (9) the wavelength of Yb‐based fiber lasers. The incorporation of an α,β′‐pyridine moiety into expanded porphyrins opens a highly interesting area of research due to the attractive optical and coordination properties of the resulting molecules.
Open Access
A review of the effect of skin pigmentation on pulse oximeter accuracy
(IOP Publishing, 2023-06-01) Al-Halawani, Raghda; Charlton, Peter H; Qassem, Meha; Kyriacou, Panayiotis A; Al-Halawani, Raghda [0000-0002-6193-921X]; Charlton, Peter H [0000-0003-3836-8655]; Qassem, Meha [0000-0003-0730-3189]; Kyriacou, Panayiotis A [0000-0002-2868-485X]
Objective. Pulse oximetry is a non-invasive optical technique used to measure arterial oxygen saturation (SpO2) in a variety of clinical settings and scenarios. Despite being one the most significant technological advances in health monitoring over the last few decades, there have been reports on its various limitations. Recently due to the Covid-19 pandemic, questions about pulse oximeter technology and its accuracy when used in people with different skin pigmentation have resurfaced, and are to be addressed. Approach. This review presents an introduction to the technique of pulse oximetry including its basic principle of operation, technology, and limitations, with a more in depth focus on skin pigmentation. Relevant literature relating to the performance and accuracy of pulse oximeters in populations with different skin pigmentation are evaluated. Main Results. The majority of the evidence suggests that the accuracy of pulse oximetry differs in subjects of different skin pigmentations to a level that requires particular attention, with decreased accuracy in patients with dark skin. Significance. Some recommendations, both from the literature and contributions from the authors, suggest how future work could address these inaccuracies to potentially improve clinical outcomes. These include the objective quantification of skin pigmentation to replace currently used qualitative methods, and computational modelling for predicting calibration algorithms based on skin colour.
Open Access
NMR Methodology for Measuring Dissolved O₂ and Transport in Lithium–Air Batteries
(American Chemical Society (ACS), 2023-06-01) Wang, Evelyna; Jónsson, Erlendur; Grey, Clare P; Wang, Evelyna [0000-0002-5697-474X]; Grey, Clare P [0000-0001-5572-192X]
Similar to fuel cells, poor mass transport of redox active species, such as dissolved oxygen gas, is one of the challenges faced by lithium–air batteries (LABs). Capitalizing on the paramagnetic properties of O2, we used nuclear magnetic resonance (NMR) spectroscopy to measure oxygen concentration and transport in LAB electrolytes. Lithium bis(trifluoromethane) sulfonylimide (LiTFSI) in glymes or dimethyl sulfoxide (DMSO) solvents were investigated with 1H, 13C, 7Li, and 19F NMR spectroscopy, with the results showing that both the 1H, 13C, 7Li, and 19F bulk magnetic susceptibility shifts and the change in 19F relaxation times were accurate measures of dissolved O2 concentration. O2 saturation concentrations and diffusion coefficients were extracted that are comparable to values measured by electrochemical or pressure methods reported in the literature, highlighting the validity of this new methodology. This method also provides experimental evidence of the local O2 solvation environment, with results again comparable to previous literature and supported by our molecular dynamics simulations. A preliminary in situ application of our NMR methodology is demonstrated by measuring O2 evolution during LAB charging using LiTFSI in the glyme electrolyte. While the in situ LAB cell showed poor coulombic efficiency, since no additives were used, the O2 evolution was successfully quantified. Our work demonstrates the first usage of this NMR methodology to quantify O2 in LAB electrolytes, experimentally demonstrate solvation environments of O2, and detect O2 evolution in situ in a LAB flow cell.
Open Access
The faecal microbiome of Exmoor ponies shows step‐wise compositional changes with increasing levels of management by humans
(2023-06-02) Bull, Katie; Davies, Gareth; Jenkins, Timothy P.; Peachey, Laura; Bull, Katie [0000-0002-6681-2162]
Background: Horses can suffer from gastrointestinal (GI) disease in domestic environments, often precipitated by human‐led changes in management. Understanding the consequences of these changes on equine gut microbiota is key to the prevention of such disease episodes. Objective: Profile the faecal microbiota of adult female Exmoor ponies under three management conditions, representing increasing levels of management by humans, encompassing different diets; whilst controlling for age, breed and sex. Study design: Cross‐sectional descriptive. Methods: Faecal samples were collected from three populations of Exmoor ponies kept under contrasting management conditions: 29 adult female ponies in groups with low management (LM) (n = 10), medium management (MM) (n = 10) and high management (HM) (n = 9) levels, based on diet, drug use, handling and exercise. Faecal microbial composition was profiled via high‐throughput sequencing of the bacterial 16S rRNA gene, and functional metagenome predictions. Results: We observed profound step‐wise changes in microbiome structure in the transition from LM to MM to HM. A relatively high abundance of Proteobacteria and Tenericutes was associated with the HM group; higher abundance of Methanobacteria was observed in the LM group. The MM group had intermediate levels of these taxa and exhibited high ‘within group’ variation in alpha diversity. Functional predictions revealed increased amino acid and lipid metabolism in HM; energy metabolism in LM and carbohydrate metabolism and immune/metabolic disease pathways in MM. Main limitations: Low group sizes, incomplete knowledge of bacterial genomes in equine gut microbiota and it was not possible to assess the relative impact of diet, drug use, handling and exercise on the microbiome as variables were confounded. Conclusions: Human‐led management factors had profound step‐wise effects on faecal microbial composition. Based on functional metagenome predictions, we hypothesise that dietary differences between groups were the major driver of observed differences.
Open Access
Development of cancer surveillance guidelines in ataxia telangiectasia: A Delphi-based consensus survey of international experts.
(2023-06-02) Neves, Renata; De Dios Perez, Blanca; Panek, Rafal; Jagani, Sumit; Wilne, Sophie; Bhatt, Jayesh M; Caputi, Caterina; Cirillo, Emilia; Coman, David J; Dückers, Gregor; Gilbert, Donald L; Kay Koenig, Mary; Mansour, Lobna; McDermott, Elizabeth; Pauni, Micaela; Pignata, Claudio; Perlman, Susan L; Porras, Oscar; Betina Porto, Mariela; Schon, Katherine; Soler-Palacin, Pere; Nick Russo, Sam; Takagi, Masatoshi; Tischkowitz, Marc; Wainwright, Claire; Dandapani, Madhumita; Glazebrook, Cristine; Suri, Mohnish; Whitehouse, William P; Dineen, Robert A; Neves, Renata [0000-0001-8835-2366]; Gilbert, Donald L [0000-0002-9245-6878]; Takagi, Masatoshi [0000-0002-7580-9184]
BACKGROUND/OBJECTIVES: Ataxia telangiectasia (A-T) is a multiorgan disorder with increased vulnerability to cancer. Despite this increased cancer risk, there are no widely accepted guidelines for cancer surveillance in people affected by A-T. We aimed to understand the current international practice regarding cancer surveillance in A-T and agreed-upon approaches to develop cancer surveillance in A-T. DESIGN/METHODS: We used a consensus development method, the e-Delphi technique, comprising three rounds. Round 1 consisted of a Delphi questionnaire and a survey that collected the details of respondents' professional background, experience, and current practice of cancer surveillance in A-T. Rounds 2 and 3 were designed based on previous rounds and modified according to the comments made by the panellists. The pre-specified consensus threshold was ≥75% agreement. RESULTS: Thirty-five expert panellists from 13 countries completed the study. The survey indicated that the current practice of cancer surveillance varies widely between experts and centres'. Consensus was reached that evidence-based guidelines are needed for cancer surveillance in people with A-T, with separate recommendations for adults and children. Statements relating to the tests that should be included, the age for starting and stopping cancer surveillance and the optimal surveillance interval were also agreed upon, although in some areas, the consensus was that further research is needed. CONCLUSION: The international expert consensus statement confirms the need for evidence-based cancer surveillance guidelines in A-T, highlights key features that the guidelines should include, and identifies areas of uncertainty in the expert community. This elucidates current knowledge gaps and will inform the design of future clinical trials.
Open Access
Template Pore Size and A‐Site Cation Management Dictate Luminescence Efficiency, Stability, and Wavelength in Confined Perovskite Nanostructures
(2023-06-01) da Costa, Viviana C. P.; Frohna, Kyle; Stranks, Samuel D.; Coffer, Jeffery L.; Coffer, Jeffery L. [0000-0003-0267-9646]
A‐site cation composition is a useful lever in optimizing the photophysical properties and stability of metal halide perovskites (MHPs). Independent of this, straightforward preparative routes to MHP nanostructures that employ a single solid‐state template with modest thermal requirements are also in demand. Here both strategies are employed in the fabrication and evaluation of luminescence properties of mixed formamidinium/cesium (Cs x FA1− x PbBr3) and methylammonium/cesium (Cs x MA1− x PbBr3) nanostructures formed within confining mesoporous silica of 4 and 7 nm average pore diameters. Use of such small‐pore oxide‐terminated templates produce perovskite nanostructures in the strongly confined regime, with broadly tunable emission from green to sky blue. It is found that the smallest nanostructures that are formamidinium rich exhibit the largest photoluminescence quantum efficiency values, but such values diminish by more than 50% in a 10 day period. In contrast, the same nanostructures formed within a 7 nm porous template retain their efficiency values over the same time window. The likely origins of this size‐dependent behavior are discussed in terms of pore‐size‐dependent capillary forces. Such routes may ultimately lead to improved light‐emitting diode designs composed of controlled quantum‐confined perovskites of greater intrinsic stability than other emitters such as ligand‐based colloidal nanocrystals.
Open Access
Existential insecurity and deference to authority: the pandemic as a natural experiment
(Frontiers Media S.A., 2023-05-19) Foa, Roberto Stefan; Welzel, Christian
Introduction: The global coronavirus pandemic offers a quasi-experimental setting for understanding the impact of sudden exposure to heightened existential risk upon both individual and societal values. Methods: We examined the effect of the pandemic on political attitudes by comparing data from eight countries surveyed before and after the worldwide spread of COVID-19 in March 2020 with continuous weekly polling tracker data from the United Kingdom from 2019 to 2021. Multilevel models were used to explore the drivers of change, and the results indicated that reported emotions of fear and stress were positively associated with institutional approval during periods of greater pathogen risk. Results: Our findings revealed that support for political and technocratic authority, as well as satisfaction with political institutions, rose significantly above long-term historical baselines during the pandemic. Discussion: The results support the hypothesis that exposure to existential risk results in greater support for authority and that individual feelings of insecurity may be linked to less critical citizen orientations.
Open Access
Identifying the Environmental Determinants of Lung Cancer: A Case Study of Henan, China
(American Geophysical Union (AGU), 2023-06) Liu, Yan; Xu, Yanqing; Li, Yuchen; Wei, Haitao; Xu, Yanqing [0000-0002-5004-9975]; Li, Yuchen [0000-0003-1670-3782]; Wei, Haitao [0000-0003-0019-6210]
Lung cancer has become one of the most prevalent cancers in the last several decades. Studies have documented that most cases of lung cancer are caused by inhaling environmental carcinogens while how external environmental factors lead to individual lung cancer is still an open issue as the pathogenesis may come from the combined action of multiple environmental factors, and such pathogenic mechanism may vary from region to region. Based on the data of lung cancer cases from hospitals at the county level in Henan from 2016 to 2020, we analyzed the response relationship between lung cancer incidence and physical ambient factors (air quality, meteorological conditions, soil vegetation) and socioeconomic factors (occupational environment, medical level, heating mode, smoking behavior). We used a Bayesian spatio‐temporal interaction model to evaluate the relative risk of disease in different regions. The results showed that smoking was still the primary determinant of lung cancer, but the influence of air quality was increasing year by year, with meteorological conditions and occupational environment playing a synergistic role in this process. The high‐risk areas were concentrated in the plains of East and Central Henan and the basin of South Henan, while the low‐risk areas were concentrated in the hilly areas of North and West Henan, which were related to the topography of Henan. Our study provides a better understanding of the environmental determinants of lung cancer which will help refine existing prevention strategies and recognize the areas where actions are required to prevent environment and occupation related lung cancer.

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