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Abstract Pituitary tumours are surrounded by critical neurovascular structures and identification of these intra-operatively can be challenging. We have previously developed an AI model capable of sellar anatomy segmentation. This study aims to apply this model, and explore the impact of AI-assistance on clinician anatomy recognition. Participants were tasked with labelling the sella on six images, initially without assistance, then augmented by AI. Mean DICE scores and the proportion of annotations encompassing the centroid of the sella were calculated. Six medical students, six junior trainees, six intermediate trainees and six experts were recruited. There was an overall improvement in sella recognition from a DICE of score 70.7% without AI assistance to 77.5% with AI assistance (+6.7; p

Abstract This paper presents the design and development of a coastal fisheries monitoring system that harnesses artificial intelligence technologies. Application of the system across the Pacific region promises to revolutionize coastal fisheries management. The program is built on a centralized, cloud-based monitoring system to automate data extraction and analysis processes. The system leverages YoloV4, OpenCV, and ResNet101 to extract information from images of fish and invertebrates collected as part of in-country monitoring programs overseen by national fisheries authorities. As of December 2023, the system has facilitated automated identification of over six hundred nearshore finfish species, and automated length and weight measurements of more than 80,000 specimens across the Pacific. The system integrates other key fisheries monitoring data such as catch rates, fishing locations and habitats, volumes, pricing, and market characteristics. The collection of these metrics supports much needed rapid fishery assessments. The system’s co-development with national fisheries authorities and the geographic extent of its application enables capacity development and broader local inclusion of fishing communities in fisheries management. In doing so, the system empowers fishers to work with fisheries authorities to enable data-informed decision-making for more effective adaptive fisheries management. The system overcomes historically entrenched technical and financial barriers in fisheries management in many Pacific island communities.

Abstract Ab initio calculations in forsterite (Mg $$_2$$ 2 SiO $$_4$$ 4 ) are used to gain insight into the formation of point defects and incorporation of noble gases. We calculate the enthalpies of incorporation both at pre-existing vacancies in symmetrically non-equivalent sites, and at interstitial positions. At high pressure, most structural changes affect the MgO $$_{6}$$ 6 units and the enthalpies of point defects increase, with those involving Mg and Si vacancies increasing more than those involving O sites. At 15 GPa Si vacancies and Mg interstitials have become the predominant intrinsic defects. We use these calculated enthalpies to estimate the total uptake of noble gases into the bulk crystal as a function of temperature and pressure both in the presence and absence of other heterovalent trace elements. For He and Ne our calculated solubilities point to atoms occupying mainly interstitial sites in agreement with previous experimental work. In contrast, Ar most likely substitutes for Mg due to its larger size and the deformation it causes within the crystal. Incorporation energies, as well as atomic distances suggest that the incorporation mainly depend on the size mismatch between host and guest atoms. Polarization effects arising from the polarizability of the noble gas atom or the presence of charged defects are minimal and do not contribute significantly to the uptake. Finally, the discrepancies between our results and recent experiments suggest that there are other incorporation mechanisms such as adsorption at internal and external interfaces, voids and grain boundaries which must play a major role in noble gas storage and solubility.

Abstract The capability to design, manufacture and test Hypersonic Glide Vehicles (HGVs) has been demonstrated by a number of nations, and they are increasingly forming part of military inventories, potentially offering capabilities highly unique to this technology. This article reports the simulated Monostatic Radar Cross Section of a generic HGV in five frequency ranges, HF, VHF, UHF, L, and S‐bands associated with different radar types. Full spherical datasets of complex co‐ and cross‐polar data are synthesised so that backscatter resulting from illumination by r.f./microwave energy of linear or circular polarisation can subsequently be computed from the raw dataset. Circular polarisation is commonly employed by ground‐based Ballistic Missile Early Warning Systems and Space Object Surveillance and Identification radars to avoid polarisation mis‐match losses resulting from ionospheric Faraday rotation effects. The data was generated using Ansys' Finite Element Solver at 10, 150 and 430 MHz, with the Geometric Optics/Physical Optics based SBR+ solver employed for 1.3 and 3 GHz data. All data was produced at below the Nyquist sampling interval relevant to the target's electrical size. These datasets were then imported into a Matlab routine which extracted data over limited angular ranges associated with the likely radar line‐of‐sight in particular scenarios, typically having a standard deviation of ±10° about the direction of flight, applying either a Gaussian or Uniform sampling distribution as part of a Monte Carlo analysis. These extracted data were then used to form histograms giving the probability of sampling particular RCS values. Probability density functions and cumulative distribution functions were then fitted, to aid in the representation of statistical target fluctuations for each band and angular sampling range. The HGV exists in either the ‘Rayleigh’, ‘resonance’ or ‘optical’ scattering regimes, depending on its relative electrical size. The results suggest that for this target shape at HF and VHF cases a simple Swerling 0 (fluctuation invariant) approximation is adequate in most instances, whilst a Gamma distribution may be applied for UHF band cases. At L and S‐band a Beta distribution was found to provide a good fit to the available data.

Abstract The molecular identification of tissue proteoforms by top-down mass spectrometry (TDMS) is significantly limited by throughput and dynamic range. We introduce AutoPiMS, a single-ion MS based multiplexed workflow for top-down tandem MS (MS2) directly from tissue microenvironments in a semi-automated manner. AutoPiMS directly off human ovarian cancer sections allowed for MS2 identification of 73 proteoforms up to 54 kDa at a rate of

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time. Cross- and side-bridged tetraazamacrocylic complexes offer significant advantages over the non-bridged molecular structures in terms of receptor affinity, potential for radiolabelling, and use in therapeutic applications. Our investigation has been extended to the influence of the ring size on bridged tetraazamacrocyclic compounds with the addition of two novel chelators (bis-cross-bridged homocyclen and bis-cross-bridged cyclen) to compare to the bis-bridged cyclam, along with novel metal complexes formed with copper(II) or zinc(II). The in vitro biological assays showed that all of the zinc(II) complexes are high affinity antagonists with a marked increase in CXCR4 selectivity for the bis-cross-bridged cyclen complex, whereas the properties of the copper(II) complexes are highly dependent on metal ion geometry. X-ray crystal structural data and DFT computational studies allow for the rationalisation of the relative affinities and the aspartate residue interactions on the protein surface. Changing the ring size from 14-membered can increase the selectivity for the CXCR4 receptor whilst retaining potent inhibitory activity, improving the key pharmacological characteristics.

IntroductionAutomation of routine clinical data shows promise in relieving health systems of the burden associated with manual data collection. Identifying consistent points of documentation in the electronic health record (EHR) provides salient targets to improve data entry quality. Using our pituitary surgery service as an exemplar, we aimed to demonstrate how process mapping can be used to identify reliable areas of documentation in the patient pathway to target structured data entry interventions.Materials and methodsThis mixed methods study was conducted in the largest pituitary centre in the UK. Purposive snowball sampling identified frontline stakeholders for process mapping to produce a patient pathway. The final patient pathway was subsequently validated against a real-world dataset of 50 patients who underwent surgery for pituitary adenoma. Events were categorized by frequency and mapped to the patient pathway to determine critical data points.ResultsEighteen stakeholders encompassing all members of the multidisciplinary team (MDT) were consulted for process mapping. The commonest events recorded were neurosurgical ward round entries (N = 212, 14.7%), pituitary clinical nurse specialist (CNS) ward round entries (N = 88, 6.12%) and pituitary MDT treatment decisions (N = 88, 6.12%) representing critical data points. Operation notes and neurosurgical ward round entries were present for every patient. 43/44 (97.7%) had a pre-operative pituitary MDT entry, pre-operative clinic letter, a post-operative clinic letter, an admission clerking entry, a discharge summary, and a post-operative histopathology pituitary multidisciplinary (MDT) team entries.ConclusionThis is the first study to produce a validated patient pathway of patients undergoing pituitary surgery, serving as a comparison to optimise this patient pathway. We have identified salient targets for structured data entry interventions, including mandatory datapoints seen in every admission and have also identified areas to improve documentation adherence, both of which support movement towards automation.

Abstract Objective Patients with rheumatoid arthritis (RA) have shown increased levels of neutrophils generating kallikrein-kinin peptides in blood which are potent mediators of inflammation. This study investigated the association between the bioregulation of kinin-mediated inflammation with the clinical, quality of life, and imaging characteristics (e.g. ultrasonography) of different arthritides. Methods Patients with osteoarthritis (OA, n = 29), gout (n = 10) and RA (n = 8) were recruited and screened for clinical symptoms, quality of life, and ultrasonographical assessment of arthritis. Blood neutrophils were assessed for the expression of bradykinin receptors (B1R and B2R), kininogens and kallikreins by immunocytochemistry with visualization by bright field microscopy. Levels of plasma biomarkers were measured by ELISA and cytometric bead array. Results Quality of life (SF-36 domains and summary scores; including pain; and, HAQ) was similar across OA, gout and RA patients; with the exception of worse physical functioning scores between OA and gout patients. Synovial hypertrophy (on ultrasound) differed between groups (p = 0.001), and the dichotomised Power Doppler (PD) score of greater than or equal to 2 (PD-GE2) was marginally significant (p = 0.09). Plasma IL-8 were highest in patients with gout followed by RA and OA (both, P

Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called “bottom-up” proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, “Top-down” proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT.

Abstract Vocal learning occurs in three clades of birds: hummingbirds, parrots, and songbirds. Examining vocal communication within the Falconiformes (sister taxon to the parrot/songbird clade) may offer information in understanding the evolution of vocal learning. Falcons are considered non-vocal learners and variation in vocalization may only be the result of variation in anatomical structure, with size as the major factor. We measured syringes in seven Falco species in the collection at the American Museum of Natural History and compiled data on weight, wing length, and tail length. Audio recordings were downloaded from several libraries and the peak frequency and frequency slope per harmonic number, number of notes in each syllable, number of notes per second, duration of each note, and inter-note duration was measured. Mass, wing length, and syringeal measurements were strongly, positively correlated, and maximum frequency is strongly, negatively correlated with the size. Frequency slope also correlates with size, although not as strongly. Both note and inter-note length vary significantly among the seven species, and this variation is not correlated with size. Maximum frequency and frequency slope can be used to identify species, with the possibility that bird sounds could be used to identify species in the field in real time.

Background: The indications for operative management of pediatric perineal injuries are debated. We aimed to investigate our institution's experience with perineal injuries in girls and identify factors for which patients require examination under anesthesia (EUA). Methods: All female pediatric patients presenting to our institution June 2015–2021 with an isolated perineal injury were reviewed. Demographics, symptoms, exam findings, Genitourinary Injury Score (GIS), and management strategy were recorded and analyzed. Patients were divided based on level of intervention – bedside examination without sedation, Emergency Department (ED) exam with sedation, or EUA. Results: In total, 202 patients with a median age of 6 years were analyzed. Bleeding was reported most frequently by patients and families (90.1%), but only 27.2% of patients had bleeding noted on ED exam. Over half of patients (n = 110, 54.5%) were managed nonoperatively; the remaining 92 (45.5%) underwent EUA. The majority of patients (n = 150, 74.3%) had a GIS of I. EUA patients had a higher estimated median total injury size (2.5 (1.5–3.5) cm vs 1.0 (0.5–1.5) cm, p < 0.001), higher percentage of active bleeding (53.3% vs. 4.8%), and higher GIS (≥ II). No one discharged from the ED required operative intervention at a later time. Conclusion: Although further prospective evaluation is required, our investigation suggests the majority of patients presenting with perineal injuries can be managed in the emergency department, but operative intervention should be considered for patients presenting with active bleeding on physical exam, laceration or hematoma > 2 cm, or GIS ≥ II.

The ability to tune band gaps of semiconductors is important for many optoelectronics applications including photocatalysis. A common approach to this is doping, but this often has the disadvantage of introducing defect states in the electronic structure that can result in poor charge mobility and increased recombination losses. In this work, density functional theory calculations are used to understand how co-doping and solid solution formation can allow tuning of semiconductor band gaps through indirect effects. The addition of ZnS to GaP alters the local environments of the Ga and P atoms, resulting in shifts in the energies of the P and Ga states that form the valence and conduction band edges, and hence changes the band gap without altering which atoms form the band edges, providing an explanation for previous experimental observations. Similarly, N doping of ZnO is known from previous experimental work to reduce the band gap and increase visible-light absorption; here we show that, when co-doped with Al, the Al changes the local environment of the N atoms, providing further control of the band gap without introducing new states within the band gap or at the band edges, while also providing an energetically more favourable state than N-doped ZnO. Replacing Al with elements of different electronegativity is an additional tool for band gap tuning, since the different electronegativities correspond to different effects on the N local environment. The consistency in the parameters identified here that control the band gaps across the various systems studied indicates some general concepts that can be applied in tuning the band gaps of semiconductors, without or only minimally affecting charge mobility.

Abstract Microplastics are a globally pervasive pollutant with the potential to directly impact species and accumulate in ecosystems. However, there remains a relative paucity of research addressing their accumulation in freshwater ecosystems and a near absence of work in crayfish, despite their high ecological and economic importance. This study investigated the presence of microplastics in the invasive signal crayfish Pacifastacus leniusculus along a stream urbanization gradient. The results demonstrate a ubiquitous presence of microplastics in crayfish digestive tracts at all sites and provide the first evidence of microplastic accumulation in tail tissue. Evidence of a positive linear trend was demonstrated between microplastic concentration in crayfish and upstream urban area size in generalized linear models. Evidence for a positive effect of the upstream urban area and a negative effect of crayfish length on microplastic concentrations in crayfish was demonstrated in multiple generalized linear regression models. Our results extend the current understanding of microplastics presence in freshwater ecosystems and demonstrate their presence in crayfish in the wild for the first time.

BackgroundCerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis.MethodsA dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score.ResultsCSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches.ConclusionNeural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.

Twenty novel Mn, Fe, and Cu complexes of ethylene cross-bridged tetraazamacrocycles with potentially copolymerizable allyl and benzyl pendant arms were synthesized and characterized. Multiple X-ray crystal structures demonstrate the cis-folded pseudo-octahedral geometry forced by the rigidifying ethylene cross-bridge and show that two cis coordination cites are available for interaction with substrate and oxidant. The Cu complexes were used to determine kinetic stability under harsh acidic and high-temperature conditions, which revealed that the cyclam-based ligands provide superior stabilization with half-lives of many minutes or even hours in 5 M HCl at 50–90 °C. Cyclic voltammetry studies of the Fe and Mn complexes reveal reversible redox processes indicating stabilization of Fe2+/Fe3+ and Mn2+/Mn3+/Mn4+ oxidation states, indicating the likelihood of catalytic oxidation for these complexes. Finally, dye-bleaching experiments with methylene blue, methyl orange, and rhodamine B demonstrate efficient catalytic decolorization and allow selection of the most successful monomeric catalysts for copolymerization to produce future heterogeneous water purification materials.

Purpose: To develop, internally validate, and assess the utility of implementing a regression model for determining endotracheal tube (ETT) insertion depth. Research methods: We recorded height, weight, age, sex, ETT internal diameter (ID), lip marking, and tracheal position from the electronic record from a random subset of 2,000 intubated subjects obtained from 1 January 2009 to 5 May 2012. A multivariable linear regression model was constructed and validated by a nonparametric bootstrapping technique using unrestricted random sampling methods. A prospective pilot of subjects admitted to the pediatric intensive care unit requiring invasive mechanical ventilatory support was conducted from 7 January 2019 to 31 May 2019. Those with spinal and/or skeletal malformations, without a post-intubation chest-x-ray (CXR) order, or whose CXR quality impaired visualizing the carina and ETT tip, were excluded. The validated regression equation determined insertion depth. CXR following intubation determined ETT position. Demographic data were summarized. Two-tailed, one-sample binomial test of proportions assessed differences in the proportion of correct position by the equation. Main findings: Four hundred and seventy-seven subjects included in model construction yielded 10,000 independent samples for internal validation; 55% were female, and the mean age (SD) was 47 (63) months. Bias between bootstrap coefficients and refined model estimates were negligible (P < 0.01). Eleven subjects in the pilot were female (64%), mean age (SD) of 36.7 (38) months. Four protocol violations (36.4%) resulted in malposition. Subsequent repositioning per protocol resulted in 100% correct positioning (P = 0.01). Conclusion: The regression equation [0.8636 * (Ht. 0.6223)] facilitated correct ETT placement. A larger, diverse sample is required for external model validation.

IntroductionCushing’s disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing’s disease.MethodsSearches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing’s disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging.Results166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years.The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37–0.69]; p

ObjectiveDespite progress in endonasal skull-base neurosurgery, cerebrospinal fluid (CSF) rhinorrhoea remains common and significant. The CRANIAL study sought to determine 1) the scope of skull-base repair methods used, and 2) corresponding rates of postoperative CSF rhinorrhoea in the endonasal transsphenoidal approach (TSA) and the expanded endonasal approach (EEA) for skull-base tumors.MethodsA prospective observational cohort study of 30 centres performing endonasal skull-base neurosurgery in the UK and Ireland (representing 91% of adult units). Patients were identified for 6 months and followed up for 6 months. Data collection and analysis was guided by our published protocol and pilot studies. Descriptive statistics, univariate and multivariable logistic regression models were used for analysis.ResultsA total of 866 patients were included - 726 TSA (84%) and 140 EEA (16%). There was significant heterogeneity in repair protocols across centres. In TSA cases, nasal packing (519/726, 72%), tissue glues (474/726, 65%) and hemostatic agents (439/726, 61%) were the most common skull base repair techniques. Comparatively, pedicled flaps (90/140, 64%), CSF diversion (38/140, 27%), buttresses (17/140, 12%) and gasket sealing (11/140, 9%) were more commonly used in EEA cases. CSF rhinorrhoea (biochemically confirmed or requiring re-operation) occurred in 3.9% of TSA (28/726) and 7.1% of EEA (10/140) cases. A significant number of patients with CSF rhinorrhoea (15/38, 39%) occurred when no intraoperative CSF leak was reported. On multivariate analysis, there may be marginal benefits with using tissue glues in TSA (OR: 0.2, CI: 0.1-0.7, p

Aims: The dosages and efficacy of 14 ultraviolet (UV) decontamination technologies were measured against a SARS-CoV-2 surrogate virus that was dried onto different materials for laboratory and field testing.Methods and results: A live enveloped, ribonucleic acid (RNA) virus surrogate for SARS-CoV-2 was dried on stainless steel 304 (SS304), Navy Top Coat-painted SS304 (NTC), cardboard, polyurethane, polymethyl methacrylate (PMMA), and acrylonitrile butadiene styrene (ABS) materials at > 8.0 log10 plaque-forming units (PFU) per test coupon. The coupons were then exposed to UV radiation during both laboratory and field testing. Commercial and prototype UV-emitting devices were measured for efficacy: four handheld devices, three room/surface-disinfecting machines, five air disinfection devices, and two larger custom-made machines. UV device dosages ranged from 0.01 to 729 mJ cm−2. The antiviral efficacy among the different UV devices ranged from no decontamination up to nearly achieving sterilization. Importantly, cardboard required far greater dosage than SS304.Conclusion: Enormous variability in dosage and efficacy was measured among the different UV devices. Porous materials limit the utility of UV decontamination.Significance and impact of the study: UV devices have wide variability in dosages, efficacy, hazards, and UV output over time, indicating that each UV device needs independent technical measurement and assessment for product development prior to and during use.

The intertidal zone, covering the nearshore fringe of coasts and islands and extending from the high-water mark to areas that remain fully submerged, encompasses a range of habitats containing resources that are as important to modern populations as they were to humans in prehistory. Effectively bridging land and sea, intertidal environments are extremely dynamic, requiring complexity and variability in how people engaged with them in the past, much as they do in the present. Here we review and reconsider environmental, archaeological, and modern socio-ecological evidence from the Zanzibar Archipelago on eastern Africa’s Swahili coast, focusing on marine molluscs to gain insight into the trajectories of human engagement with nearshore habitats and resources. We highlight the potential drivers of change and/or stability in human-intertidal interactions through time and space, set against a backdrop of the significant socio-economic and socio-ecological changes apparent in the archipelago, and along the Swahili coast, during the late Holocene.

Abstract Background Transsphenoidal surgery is the gold standard for pituitary adenoma resection. Although rare, a serious complication of surgery is worsened vision post-operatively. Objective To determine whether, in patients undergoing transsphenoidal surgery for pituitary adenoma, intraoperative monitoring of visual evoked potentials (VEP) is a safe, reproducible, and effective technological adjunct in predicting postoperative visual function. Methods The PubMed and OVID platforms were searched between January 1993 and December 2020 to identify publications that (1) featured patients undergoing transsphenoidal surgery for pituitary adenoma, (2) used intraoperative optic nerve monitoring with VEP and (3) reported on safety or effectiveness. Reference lists were cross-checked and expert opinion sought to identify further publications. Results Eleven studies were included comprising ten case series and one prospective cohort study. All employed techniques to improve reliability. No safety issues were reported. The only comparative study included described a statistically significant improvement in post-operative visual field testing when VEP monitoring was used. The remaining case-series varied in conclusion. In nine studies, surgical manipulation was halted in the event of a VEP amplitude decrease suggesting a widespread consensus that this is a warning sign of injury to the anterior optic apparatus. Conclusions Despite limited and low-quality published evidence regarding intra-operative VEP monitoring, our review suggests that it is a safe, reproducible, and increasingly effective technique of predicting postoperative visual deficits. Further studies specific to transsphenoidal surgery are required to determine its utility in protecting visual function in the resection of complex pituitary tumours.

Human energy consumption and productivity have steeply risen around 1950 CE, leading to a departure from the Earth’s Holocene state into the Anthropocene, suggests a quantitative analysis of humanity’s influence on the Earth system.

Lysine fatty acylation is an important protein posttranslational modification but mammalian lysine fatty acyl transferases have remained unknown so far. Here the authors report that the human N-terminal glycine myristoyltransferases 1 and 2 catalyze the addition of myristoyl chains to specific lysine residues and show that they myristoylate ARF6 lysine 3, which explains the unusual membrane binding properties of ARF6.

Abstract Background Immunization with attenuated malaria sporozoites protects humans from experimental malaria challenge by mosquito bite. Protection in humans is strongly correlated with the production of T cells targeting a heterogeneous population of pre-erythrocyte antigen proteoforms, including liver stage antigens. Currently, few T cell epitopes derived from Plasmodium falciparum, the major aetiologic agent of malaria in humans are known. Methods In this study both in vitro and in vivo malaria liver stage models were used to sequence host and pathogen proteoforms. Proteoforms from these diverse models were subjected to mild acid elution (of soluble forms), multi-dimensional fractionation, tandem mass spectrometry, and top-down bioinformatics analysis to identify proteoforms in their intact state. Results These results identify a group of host and malaria liver stage proteoforms that meet a 5% false discovery rate threshold. Conclusions This work provides proof-of-concept for the validity of this mass spectrometry/bioinformatic approach for future studies seeking to reveal malaria liver stage antigens towards vaccine development.

The contribution of seafood to global food security is being increasingly highlighted in policy. However, the extent to which such claims are supported in the current food security literature is unclear. This review assesses the extent to which seafood is represented in the recent food security literature, both individually and from a food systems perspective, in combination with terrestrially-based production systems. The results demonstrate that seafood remains under-researched compared to the role of terrestrial animal and plant production in food security. Furthermore, seafood and terrestrial production remain siloed, with very few papers addressing the combined contribution or relations between terrestrial and aquatic systems. We conclude that far more attention is needed to the specific and relative role of seafood in global food security and call for the integration of seafood in a wider interdisciplinary approach to global food system research.

Ornithine aminotransferase (OAT) is overexpressed in hepatocellular carcinoma (HCC), and we previously showed that inactivation of OAT inhibits the growth of HCC. Recently, we found that (3S,4S)-3-amino-4-fluorocyclopentenecarboxylic acid (5) was a potent inactivator of γ-aminobutyric acid aminotransferase (GABA-AT), proceeding by an enamine mechanism. Here we describe our investigations into the activity and mechanism of 5 as an inactivator of human OAT. We have found that 5 exhibits 10-fold less inactivation efficiency (kinact/KI) against hOAT than GABA-AT. A comprehensive mechanistic study was carried out to understand its inactivation mechanism with hOAT. pKa and electrostatic potential calculations were performed to further support the notion that the α,β-unsaturated alkene of 5 is critical for enhancing acidity and nucleophilicity of the corresponding intermediates and ultimately responsible for the improved inactivation efficiency of 5 over the corresponding saturated analogue (4). Intact protein mass spectrometry and the crystal structure complex with hOAT provide evidence to conclude that 5 mainly inactivates hOAT through noncovalent interactions, and that, unlike with GABA-AT, covalent binding with hOAT is a minor component of the total inhibition which is unique relative to other monofluoro-substituted derivatives. Furthermore, based on the results of transient-state measurements and free energy calculations, it is suggested that the α,β-unsaturated carboxylate group of PLP-bound 5 may be directly involved in the inactivation cascade by forming an enolate intermediate. Overall, compound 5 exhibits unusual structural conversions which are catalyzed by specific residues within hOAT, ultimately leading to an enamine mechanism-based inactivation of hOAT through noncovalent interactions and covalent modification.

Background ApoAI (apolipoproteins AI) and apoAII (apolipoprotein AII) are structural and functional proteins of high‐density lipoproteins (HDL) which undergo post‐translational modifications at specific residues, creating distinct proteoforms. While specific post‐translational modifications have been reported to alter apolipoprotein function, the full spectrum of apoAI and apoAII proteoforms and their associations with cardiometabolic phenotype remains unknown. Herein, we comprehensively characterize apoAI and apoAII proteoforms detectable in serum and their post‐translational modifications and quantify their associations with cardiometabolic health indices. Methods and Results Using top‐down proteomics (mass‐spectrometric analysis of intact proteins), we analyzed paired serum samples from 150 CARDIA (Coronary Artery Risk Development in Young Adults) study participants from year 20 and 25 exams. Measuring 15 apoAI and 9 apoAII proteoforms, 6 of which carried novel post‐translational modifications, we quantified associations between percent proteoform abundance and key cardiometabolic indices. Canonical (unmodified) apoAI had inverse associations with HDL cholesterol and HDL‐cholesterol efflux, and positive associations with obesity indices (body mass index, waist circumference), and triglycerides, whereas glycated apoAI showed positive associations with serum glucose and diabetes mellitus. Fatty‐acid‒modified ApoAI proteoforms had positive associations with HDL cholesterol and efflux, and inverse associations with obesity indices and triglycerides. Truncated and dimerized proteoforms of apoAII were associated with HDL cholesterol (positively) and obesity indices (inversely). Several proteoforms had no significant associations with phenotype. Conclusions Associations between apoAI and AII and cardiometabolic indices are proteoform‐specific. These results provide “proof‐of‐concept” that precise chemical characterization of human apolipoproteins will yield improved insights into the complex pathways through which proteins signify and mediate health and disease.

Background:. The purpose of this study was to introduce a modification of the Furlow double-opposing Z-plasty (DOZ)—the square-root palatoplasty (SRP)—and critically evaluate outcomes compared to children who underwent straight-line repair (SLR). Methods:. A retrospective review was performed of all nonsyndromic children undergoing primary cleft palate closure either by SRP or SLR at our institution between 2009 and 2017. Outcomes of interest included rates/location of oronasal fistula, secondary surgery, speech delay/deficits, resonance, nasal air emission (NAE), articulation errors, and velopharyngeal function. Logistic regression was used to assess for the effect of surgery type on outcomes while controlling for Veau cleft type, age, and gender. Results:. Seventy-eight patients were included; 46 (59%) underwent SRP, and 32 (41%) underwent SLR. The mean follow-up was 4.07 years. When compared to SLR, children who underwent SRP were less likely to have oronasal fistula [odds ratio (OR) 4.8, P = 0.0159], speech delay/deficits (OR 7.7, P < 0.001), NAE (OR 9.7, P < 0.001), articulation errors (OR 10.2, P < 0.001), or need for secondary speech surgery (OR 13.2, P < 0.0002). Patients who underwent SRP were also more likely to have normal resonance (78.26% versus 43.75%, respectively; P = 0.0043) and good VP function (84.78% versus 56.25%, respectively; P = 0.0094). Conclusions:. This study describes and evaluates outcomes following a modified-Furlow DOZ technique—the SRP. After adjusting for Veau classification, age, and gender in nonsyndromic children, SRP is associated with significantly less speech delay/deficits, NAE, articulation errors, and need for secondary speech surgery when compared to children who underwent SLR.

Irreproducibility of preclinical findings could be a significant barrier to the “bench-to-bedside” development of oncolytic viruses (OVs). A contributing factor is the incomplete and non-transparent reporting of study methodology and design. Using the NIH Principles and Guidelines for Reporting Preclinical Research, a core set of seven recommendations, we evaluated the completeness of reporting of preclinical OV studies. We also developed an evidence map identifying the current trends in OV research. A systematic search of MEDLINE and Embase identified all relevant articles published over an 18 month period. We screened 1,554 articles, and 236 met our a priori-defined inclusion criteria. Adenovirus (43%) was the most commonly used viral platform. Frequently investigated cancers included colorectal (14%), skin (12%), and breast (11%). Xenograft implantation (61%) in mice (96%) was the most common animal model. The use of preclinical reporting guidelines was listed in 0.4% of articles. Biological and technical replicates were completely reported in 1% of studies, statistics in 49%, randomization in 1%, blinding in 2%, sample size estimation in 0%, and inclusion/exclusion criteria in 0%. Overall, completeness of reporting in the preclinical OV therapy literature is poor. This may hinder efforts to interpret, replicate, and ultimately translate promising preclinical OV findings. Keywords: oncolytic virus, reporting guidelines, preclinical study design, reproducibility, methodological rigor, reporting standards, transparency, reporting quality, immunotherapy

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

Abstract The term Anthropocene initially emerged from the Earth System science community in the early 2000s, denoting a concept that the Holocene Epoch has terminated as a consequence of human activities. First associated with the onset of the Industrial Revolution, it was then more closely linked with the Great Acceleration in industrialization and globalization from the 1950s that fundamentally modified physical, chemical, and biological signals in geological archives. Since 2009, the Anthropocene has been evaluated by the Anthropocene Working Group, tasked with examining it for potential inclusion in the Geological Time Scale. Such inclusion requires a precisely defined chronostratigraphic and geochronological unit with a globally synchronous base and inception, with the mid‐twentieth century being geologically optimal. This reflects an Earth System state in which human activities have become predominant drivers of modifications to the stratigraphic record, making it clearly distinct from the Holocene. However, more recently, the term Anthropocene has also become used for different conceptual interpretations in diverse scholarly fields, including the environmental and social sciences and humanities. These are often flexibly interpreted, commonly without reference to the geological record, and diachronous in time; they often extend much further back in time than the mid‐twentieth century. These broader conceptualizations encompass wide ranges and levels of human impacts and interactions with the environment. Here, we clarify what the Anthropocene is in geological terms and compare the proposed geological (chronostratigraphic) definition with some of these broader interpretations and applications of the term “Anthropocene,” showing both their overlaps and differences.

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Aims: To develop infectious (live/dead) enveloped virus test indicators and response surface methodology (RSM) models that evaluate survival of an enveloped ribonucleic acid (RNA) virus on contaminated aircraft materials after exposure to hot, humid air (HHA).Methods and Results: Enveloped RNA bacteriophage Phi6 (Φ6) was dried on wiring insulation, aircraft performance coating (APC), polypropylene, and nylon at ≥ 8 log10 plaque-forming units (PFU) test coupon−1. Only 2.4 log10 inactivation was measured on APC at 70°Celsius (°C), 5% relative humidity (RH) after 24 h. In contrast, HHA RSM models showed a 90% probability of a 7 log10 inactivation at ≥63°C, 90% RH after 1 h, and decontamination kinetics were similar across different materials. HHA decontamination of C-130 and C-17 aircraft showed >7 log10 and ≥5.9 log10 inactivation of enveloped virus on 100 and 110 test indicators, respectively, with a 1-h treatment, excluding ramp-up and ramp-down times.Conclusions: Enveloped RNA virus test indicators were successfully developed, lab tested for HHA decontamination, analyzed for RSM, and field-tested in aircraft demonstrations.Significance and Impact of the Study: The utility of HHA decontamination was demonstrated after inactivating enveloped RNA virus on aircraft with a 1-h HHA treatment within aircraft temperature and RH limits.

While the ubiquity and rising abundance of microplastic contamination is becoming increasingly well-known, there is very little empirical data for the scale of their historical inputs to the environment. For many pollutants, where long-term monitoring is absent, paleoecological approaches (the use of naturally-accumulating archives to assess temporal trends) have been widely applied to determine such historical patterns, but to date this has been undertaken only very rarely for microplastics, despite the enormous potential to identify the scale and extent of inputs as well as rates of change. In this paper, we briefly assess the long-term monitoring and paleoecological microplastic literature before considering the advantages and disadvantages of various natural archives (including lake and marine sediments, ice cores and peat archives) as a means to determine historical microplastic records, as well as the range of challenges facing those attempting to extract microplastics from them. We also outline some of the major considerations in chemical, physical and biological taphonomic processes for microplastics as these are critical to the correct interpretation of microplastic paleoecological records but are currently rarely considered. Finally, we assess the usefulness of microplastic paleoecological records as a stratigraphic tool, both as a means to provide potential chronological information, as well as a possible marker for the proposed Anthropocene Epoch.

ABSTRACT Advances in genome sequencing have revitalized natural product discovery efforts, revealing the untapped biosynthetic potential of fungi. While the volume of genomic data continues to expand, discovery efforts are slowed due to the time-consuming nature of experiments required to characterize new molecules. To direct efforts toward uncharacterized biosynthetic gene clusters most likely to encode novel chemical scaffolds, we took advantage of comparative metabolomics and heterologous gene expression using fungal artificial chromosomes (FACs). By linking mass spectral profiles with structural clues provided by FAC-encoded gene clusters, we targeted a compound originating from an unusual gene cluster containing an indoleamine 2,3-dioxygenase (IDO). With this approach, we isolate and characterize R and S forms of the new molecule terreazepine, which contains a novel chemical scaffold resulting from cyclization of the IDO-supplied kynurenine. The discovery of terreazepine illustrates that FAC-based approaches targeting unusual biosynthetic machinery provide a promising avenue forward for targeted discovery of novel scaffolds and their biosynthetic enzymes, and it also represents another example of a biosynthetic gene cluster “repurposing” a primary metabolic enzyme to diversify its secondary metabolite arsenal. IMPORTANCE Here, we provide evidence that Aspergillus terreus encodes a biosynthetic gene cluster containing a repurposed indoleamine 2,3-dioxygenase (IDO) dedicated to secondary metabolite synthesis. The discovery of this neofunctionalized IDO not only enabled discovery of a new compound with an unusual chemical scaffold but also provided insight into the numerous strategies fungi employ for diversifying and protecting themselves against secondary metabolites. The observations in this study set the stage for further in-depth studies into the function of duplicated IDOs present in fungal biosynthetic gene clusters and presents a strategy for accessing the biosynthetic potential of gene clusters containing duplicated primary metabolic genes.