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SARS-CoV-2’s genetic plasticity has led to several variants of concern (VOCs). Here we studied replicative capacity for seven SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, and Omicron BA.1) in primary reconstituted airway epithelia (HAE) and lung-derived cell lines. Furthermore, to investigate the host range of Delta and Omicron compared to ancestral SARS-CoV-2, we assessed replication in 17 cell lines from 11 non-primate mammalian species, including bats, rodents, insectivores and carnivores. Only Omicron’s phenotype differedin vitro, with rapid but short replication and efficient production of infectious virus in nasal HAEs, in contrast to other VOCs, but not in lung cell lines. No increased infection efficiency for other species was observed, but Delta and Omicron infection efficiency was increased in A549 cells. Notably replication in A549 and Calu3 cells was lower than in nasal HAE. Our results suggest better adaptation of VOCs towards humans, without an extended host range.

Producers of PDO (Protected Designation of Origin) wines must submit to the EU authorities’ technical specifications that include the specific sensory description of each product typology, to be subsequently checked by the competent authority in each country. Unfortunately, there is no consensual and standardized approach for the development of sensory control methods for PDO wines. The aim of this work was to develop a sensory profile for the taste and mouthfeel descriptors that allows the characterization of wines from 11 existing PDOs in Catalonia (Spain), and with the purpose of advancing the process of harmonization of the official sensory analysis of wines. This paper includes the selection process of tasters, the procedure used for the definition and grouping of descriptors, and the development of references for the selected attributes. The use of this analytical tool should allow PDO/PGI product certification and control authorities to verify compliance with their specifications (descriptive and quantitative) based on objectively evaluated results. This research was funded by the project MINORVIN “Valorization of minority grape varieties for their capacity to diversify viticulture and oenology and to minimize the effects of climate change in wine quality,” RTI2018-101085-R-C33 (MICINN/AEI/ERDF, EU).

OBJECTIVES: To evaluate the performance of 4-dimensional computed tomography (4D-CT) in assessing upper airway obstruction (UAO) in patients with Robin Sequence (RS) and compare the accuracy and reliability of 4D-CT and flexible fiberoptic laryngoscopy (FFL). STUDY DESIGN: Prospective survey of retrospective clinical data. SETTING: Single, tertiary care pediatric hospital. METHODS: At initial and 30-day timepoints, a multidisciplinary group of 11 clinicians who treat RS rated UAO severity in 36 sets of 4D-CT visualizations and FFL videos (dynamic modalities), and static CT images. Raters assessed UAO at the velopharynx and oropharynx (1-none to 5-complete) and noted confidence levels (LOC) of each rating. Intraclass correlation and Krippendorff’s Alpha were used to assess intra- and inter-rater reliability, respectively. Accuracy was assessed by comparing clinician ratings with Quantitative Percent Constriction (QPC) Ratings, calculated based on 4D-CT airway cross-sectional area. Results were compared using Wilcoxon rank-sum and signed-rank tests. RESULTS: 4D-CT and FFL demonstrated similar intra-rater agreement (moderate to substantial) and both demonstrated fair inter-rater agreement. Both modalities underestimated UAO severity, though 4D-CT ratings were significantly more accurate, as determined by QPC similarity, than FFL (−1.06 and −1.46 vs QPC Ratings, p=0.004). Overall LOC was similar for 4D-CT and FFL, but other specialists were significantly less confident in FFL ratings than were otolaryngologists (2.25 and 3.92, p

Artificial intelligence (AI) is a broad and complicated concept that has begun to affect many areas of medicine, perhaps none so much as radiology. While pediatric radiology has been less affected than other radiology subspecialties, there are some well-developed and some nascent applications within the field. This review focuses on the use of AI within pediatric radiology for image interpretation, with descriptive summaries of the literature to date. We highlight common features that enable successful application of the technology, along with some of the limitations that can inhibit the development of this field. We present some ideas for further research in this area and challenges that must be overcome, with an understanding that technology often advances in unpredictable ways.

Walking underwater reduces joint impacts, enhances stability and lowers the net body weight of the patient during rehabilitation. It is a recent rehabilitation method and few suitable methods exist to study underwater gait kinematics. We propose an underwater inertial measurement (IMU) system analogous to those used in land-based rehabilitation to investigate gait kinematics. The objective of this study was to test and validate the proposed system in two human trials by evaluating the knee angle during the gait. In the first trial, a three-way performance analysis was carried out between the IMU, optoelectronic and motion-capture systems in a traditional rehabilitation setting on land. In the second trial, the proposed underwater IMU is compared with camera-based motion-capture both inside and outside the water environment, using the same subjects in both phases of the trial. This allows for an evaluation of the walking gait in air and underwater as well as a cross-comparison of IMU-based knee angle estimates before and after Gaussian Process Regression. The major finding of this work is that the proposed underwater wearable IMU system provides reliable and repeatable measurements of the knee angle during the gait, both in air and underwater.

A normal sagittal vertical axis (SVA) after spinal deformity correction can yield mechanical complications of up to 30%. Post-operative compensatory pelvic orientation can produce a normal SVA. We assess relative pelvic version (RPV), an individualised measure, for persistent post-operative compensatory measures.Adult spinal deformity (ASD) patients who were treated operatively, with a normal SVA ( ± 50 mm) at 6-week follow-up were included, who were then followed-up after 2 years. These only included patients with fusion of 4 vertebrae extending to L5 or below. Six-week subgroups were made regarding pelvis orientation, relative pelvic version (RPV: anteversion, aligned, moderate or severe retroversion) with analysis of patient-related outcome measures (PROMs), complications and spino-pelvic sagittal parameters.At 6 weeks, 140 patients met the inclusion criteria, 5 (3.6%) patients had anteversion, 59 (42.1%) were aligned, 60 (42.9%) had moderate retroversion and 16 (11.4%) patients had severe retroversion. Follow-up after 2 years demonstrated increased RPV in all groups except the severe RPV group who were more likely to develop SVA 50 mm. Complications occurred in all groups. Significant 2-year differences were observed between moderate and severe RPV for back pain and PROMs but not between other RPV groups.Adult spinal deformity patients with a normal SVA after spino-pelvic instrumentation carry a significant risk of retroversion progression post-operatively, followed by increased positive sagittal balance. Relative pelvic version (RPV) measurements when categorised into anteversion, aligned, moderate retroversion and severe retroversion at 6 weeks were predictive of PROMs at 2 years.

There remains significant variability in the use of postoperative opioids. On one end, it is proven that appropriate pain control is a critical aspect of patient management; on the other end, past few decades have been associated with major increases in opioid-related overdoses and addiction treatment. We hypothesized that several pre- and postoperative risk factors affecting long-term opioid use could be identified.Evaluation of factors associated with minimum 5-year postoperative opioid use following adult spinal deformity surgery.Prospectively followed study group database.Adult spinal deformity patients who underwent elective spine surgery between 2009 and 2016 were included.Opioid usage or otherwise at minimum 5 years follow-up. Use of nonopioid analgesics, weak and strong opioids METHODS: Retrospective analysis of patients undergoing elective spinal deformity surgery. A total of 37 factors comprising patient characteristics, radiographic measurements, operative details, preoperative and early postoperative opioid use, and mechanical complications and revisions were analyzed. Details on identified factors were provided.A total of 265 patients (215F, 50M) from five sites were included. The mean follow-up duration was 68.4±11.7 (60-102) months. On average, 10.6±3.5 levels were fused. Preoperatively, 64 (24.2%) patients were using opioids. The rate of opioid users increased to 33.6% at 6 weeks and decreased to 21.5% at 6 months. During follow-up, there were patients who discontinued opioids, while others have started and/or restarted using opioids. As a result, 59 (22.3%) patients were still on opioids at the latest follow-up. Multivariate analyses showed that factors independently affecting opioid use at an average of 68 months postoperatively, in order of significance, were opioid use at sixth weeks, preoperative opioid use and opioid use at sixth months with the odds ratios of 2.88, 2.51, and 2.38 respectively. At these time points, factors such as age, number of comorbidities, tobacco use, the time of the last prior spine surgery and postoperative sagittal plane alignment affected opioid usage rates.Opioid usage at 6 weeks was found to be more predictive of long-term opioid use compared to preoperative use. Patients should be well informed to have realistic expectations regarding opioid use when considering adult spinal deformity surgery.

Sequencing of the human genome in the early 2000s enabled probing of the genetic basis of disease on a scale previously unimaginable. Now, two decades later, after interrogating millions of markers in thousands of individuals, a significant portion of disease heritability still remains hidden. Recent efforts to unravel this 'missing heritability' have focused on garnering new insight from merging different data types, including medical imaging. Imaging offers promising intermediate phenotypes to bridge the gap between genetic variation and disease pathology. In this review we outline this fusion and provide examples of imaging genomics in a range of diseases, from oncology to cardiovascular and neurodegenerative disease. Finally, we discuss how ongoing revolutions in data science and sharing are primed to advance the field.

Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3–specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation. Significance: This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1

Isotope identification is a recurrent problem in gamma spectroscopy with high purity germanium detectors. In this work, new strategies are introduced to facilitate this type of analysis. Five criteria are used to identify the parent isotopes making a query on a large database of gamma-lines from a multitude of isotopes producing an output list whose entries are sorted so that the gamma-lines with the highest chance of being present in a sample are placed at the top. A metric to evaluate the performance of the different criteria is introduced and used to compare them. Two of the criteria are found to be superior than the others: one based on fuzzy logic, and another that makes use of the gamma relative emission probabilities. A program called histoGe implements these criteria using a SQLite database containing the gamma-lines of isotopes which was parsed from WWW Table of Radioactive Isotopes. histoGe is Free Software and is provided along with the database so they can be used to analyze spectra obtained with generic gamma-ray detectors., 12 pages, 7 tables, 7 figures

New tumor types are continuously being described with advances in molecular testing and genomic analysis resulting in better prognostics, new targeted therapy options and improved patient outcomes. As a result of these advances, pathological classification of tumors is periodically updated with new editions of the World Health Organization (WHO) Classification of Tumors books. In 2021, WHO Classification of Tumors of the Central Nervous System, 5

Objective To evaluate color, lightness, chroma, hue, and translucency adjustment potential of resin composites using CIEDE2000 color difference formula. Methods Three resin composites (Filtek Universal, Harmonize, and Omnichroma) were tested. Two types of specimens were prepared: an outer base shade with an inner hole filled with test shades and single-composite specimens of all shades. Spectrorradiometric reflectances measurements and subsequent CIELAB color coordinates and translucency parameter (TP) were performed. Color (CAP00 ), lightness, chroma, hue, and translucency (TAP00 ) adjustment potential using CIEDE2000 color difference were computed. Color and transparency differences among composite materials and shades were statistically tested (P Results Positive CAP00 and TAP00 values were found for majority of tested materials. CAP00 values ranged from -0.14 to 0.89, with the highest values found for Omnichroma (>0.75 in all cases). TAP00 values ranged from -0.06 to 0.86 with significant translucency differences among dual and single specimens. Omnichroma exhibited the highest adjustment potential for all color dimensions studied. Conclusions Lightness, hue, chroma, and translucency adjustment potential have been introduced using CIEDE2000 color difference formula, and have shown their usefulness to evaluate blending effect in dentistry. Color coordinates and translucency adjustment potential were dependent on dental material. Omnichroma exhibited the most pronounced blending effect. Clinical significance Resin composites with increased color and translucency adjustment may simplify shade selection, making this process easier and less time consuming. Furthermore, these materials might facilitate challenging and complex color matching situations.

The adeno-associated virus (AAV) non-structural Rep proteins catalyze all the DNA transactions required for virus viability including, DNA replication, transcription regulation, genome packaging, and during the latent phase, site-specific integration. Rep proteins contain two multifunctional domains: an Origin Binding Domain (OBD) and a SF3 helicase domain (HD). Studies have shown that Rep proteins have a dynamic oligomeric behavior where the nature of the DNA substrate molecule modulates its oligomeric state. In the presence of ssDNA, Rep68 forms a large double-octameric ring complex. To understand the mechanisms underlying AAV Rep function, we investigated the cryo-EM and X-ray structures of Rep68-ssDNA complexes. Surprisingly, Rep68 generates hybrid ring structures where the OBD forms octameric rings while the HD forms heptamers. Moreover, the binding to ATPγS promotes a large conformational change in the entire AAA+ domain that leads the HD to form both heptamer and hexamers. The HD oligomerization is driven by an interdomain linker region that acts as a latch to 'catch' the neighboring HD subunit and is flexible enough to permit the formation of different stoichiometric ring structures. Overall, our studies show the structural basis of AAV Rep's structural flexibility required to fulfill its multifunctional role during the AAV life cycle. ispartof: NUCLEIC ACIDS RESEARCH vol:48 issue:22 pages:12983-12999 ispartof: location:England status: published

AIM We sought to determine the frequency and patterns of delayed medical care seeking for young children with skull fractures. METHODS We identified accidental skull fractures

Diabetes deteriorates the central nervous system declining the motion capacity, mental speed and efficiency. Additionally, diabetes affects the visual system particularly the retina. Both systems are evaluated separately even though they have a direct relationship to simple tasks such as object evasion. For these reasons, the main objective of this research is to study the relationship between retinal response and the patient’s cognitive abilities. This article presents the results of experimental tests applied to 34 patients diagnosed with Type 2 Diabetes Mellitus without diabetic retinopathy. Two visual perception experiments were applied in order to evaluate the simple and choice reaction times, while the electrical response of the retina was obtained via electroretinography. The results obtained from the visual perception experiments and the retinal evaluation were correlated with the following variables: central glucose; glycosylated hemoglobin and, age. The statistical analysis of the results shows a negative correlation between glucose and the times for retinal response (ta = - 0.2109 p = 0.2548, tb = - 0.2646 p = 0.1503). A significant correlation between the simple reaction times and the retinal response times was identified (ta = 0.3141 p = 0.0800, tb = 0.2981 p = 0.0975). While no relationship between the performance index and the retinal response was found. The results indicate that the visual system plays a fundamental role in the simple reaction process and this does not influence the decision-making process.

Aim To evaluate the efficacy, safety and tolerability of a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) in patients with hypothalamic obesity (HO). Materials and Methods A two‐arm, randomized, multicentre, double‐blind, placebo‐controlled trial was conducted in 10‐ to 25‐year‐olds with hypothalamic injury following intracranial tumour and HO. Participants were randomized to once‐weekly subcutaneous injections of a GLP‐1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint was 36‐week % change in body mass index (BMI). Secondary outcomes included change in body composition (by dual energy x‐ray absorptiometry). Results Forty‐two participants were randomized to ExQW (n = 23) or placebo (n = 19). Participants were 5 ± 2 years (mean ± SD) postdiagnosis and development of HO (BMI 37.3 ± 7.1 kg/m2). In intention‐to‐treat analysis, the effect of 36‐week ExQW vs. placebo on % Δ BMI was not significant (estimated treatment difference −1.7 ± 1.8%, 95% CI −4.1 to 0.6%, P = .40); however, total body fat mass was reduced (estimated treatment difference −3.1 ± 1.4 kg, 95% CI −5.7 to −0.4 kg, P = .02). There was a significant reduction in waist circumference (estimated effect of treatment −3.5 [95% CI −5.5 to −1.6] cm, P = .004). All patients treated with placebo increased % of adipose tissue, while 50% treated with ExQW had reductions (P

The intense competition of global markets stimulates a significant change in the way products are designed, manufactured, and delivered. Such a situation is forcing companies to consider the use of new tools to support this decision process. This paper describes an agent-based system implementing a novel consumer-based fuzzy multicriteria methodology to support the design of new products. It argues that a combination of marketing decision support systems, multicriteria and multiobjective methodologies, fuzzy models, and agent technologies could be a valuable tool to assist marketing managers in new product design applications. In the multi-agent system architecture, software agents were classified into types and organized in teams. The first includes interface, task, and information agents. The second reflects Simon’s decision-making process, including intelligence, design, and choice teams. The communication between agents is carried out using an ontology. An example of system operation attempting to get the design of new corn oil is presented using sequence diagrams.

Emergency department (ED) visits for eye and vision-related concerns are common. In most cases, accurate diagnosis is made using clinical history and physical exam findings without the need for emergent imaging. When orbital imaging is performed in the ED, it is often in patients with orbital trauma where CT is used to assess for orbital fractures and associated injuries. However, CT or MR imaging can also be critical to appropriately diagnose and manage certain ED patients with nontraumatic eye and vision-related conditions. The purpose of this article is to review the imaging findings and differential diagnoses for nontraumatic orbital and neuro-ophthalmological emergencies from a practical, clinical perspective, based on a patient's typical presenting symptoms. The more commonly imaged clinical indications will be discussed including periorbital swelling, proptosis, eye pain, diplopia, and visual disturbances. In addition, rare but easily overlooked and clinically important diagnoses for the emergency radiologist to recognize will be highlighted.

Background and Purpose— Focal cerebral arteriopathy-inflammatory type (FCA-i) is a common cause of pediatric arterial ischemic stroke characterized angiographically by unifocal and unilateral stenosis/irregularity of the large anterior circulation arteries with a presumed inflammatory cause. Arterial vessel wall enhancement (VWE) on vessel wall magnetic resonance imaging is a potential biomarker of inflammation that may improve diagnosis, guide treatment, and predict outcomes in patients with FCA-i. We hypothesized that patients with FCA-i with more severe or extensive VWE would have worse arteriopathy, larger infarcts, worse clinical outcome, and increased risk for infarct progression/recurrence. Methods— Pediatric patients with arterial ischemic stroke, classified as FCA-i, and who underwent vessel wall imaging were retrospectively identified at our institution. Clinical data were reviewed and the Pediatric Stroke Outcome Measure at 1 year was determined as the primary clinical end point. Neuroimaging studies were assessed for infarct size, arteriopathy severity (Focal Cerebral Arteriopathy Severity Score), and VWE. Results— Nine cases of FCA-i with vessel wall imaging were evaluated, and there was a strong correlation between clinical outcome at 1-year with initial infarct volume (Spearman correlation coefficient rho=0.84; P P P Conclusions— VWE may not be a reliable biomarker for the diagnosis or assessment of FCA-i, and future work is needed to assess the utility of vessel wall imaging in pediatric arterial ischemic stroke and FCA-i.

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Promoting a healthy diet is a relevant strategy for preventing non-communicable diseases. This study aims to evaluate the impact of an innovative tool, the SAlBi educa nutrition app, in primary healthcare dietary counseling to improve dietary profiles as well as adherence to the Mediterranean diet. A multi-center randomized control trial comprising 104 participants was performed. Both control (n = 49) and intervention (n = 55) groups attended four once-weekly sessions focusing on healthy eating habits and physical activity, over one month. As well as attending the meetings, the intervention group used the app, which provides self-monitoring and tailored dietary advice based on the Mediterranean diet model. In a second intervention (one arm trial), the potential of SAlBi educa was evaluated for three months during the COVID-19 pandemic. At 4 weeks, the intervention group had significantly increased their carbohydrate intake (7.7% (95% CI: 0.16 to 15.2)) and decreased their total fat intake (−5.7% (95% CI: −10.4 to −1.15)) compared to the control group. Significant differences were also found for carbohydrates (3.5% (95% CI: −1.0 to 5.8)), total fats (−5.9% (95% CI: −8.9 to −3.0)), fruits and vegetables (266.3 g/day (95% CI: 130.0 to 402.6)), legumes (7.7g/day (95% CI: 0.2 to 15.1)), starchy foods (36.4 g/day (95% CI: 1.1 to 71.7)), red meat (−17.5 g/day (95% CI: −34.0 to −1.1)), and processed meat (−6.6 g/day (95% CI: −13.1 to −0.1)) intakes during the COVID-19 pandemic. SAlBi educa is a useful tool to support nutrition counseling in primary healthcare, including in special situations such as the COVID-19 pandemic. Trial registration: ISRCTN57186362. Consejería de Salud y Familia, Junta de Andalucía (Innovative Project in Health) grant number PIN-0050-2018.

This publication is part of the R&D&I project RTI2018-101674-B-I00 and was supported by by the Government of Andalusia under grants CV20-64934 and P20-00163., Differentiation between the various non-small-cell lung cancer subtypes is crucial for providing an effective treatment to the patient. For this purpose, machine learning techniques have been used in recent years over the available biological data from patients. However, in most cases this problem has been treated using a single-modality approach, not exploring the potential of the multi-scale and multi-omic nature of cancer data for the classification. In this work, we study the fusion of five multi-scale and multi-omic modalities (RNA-Seq, miRNA-Seq, whole-slide imaging, copy number variation, and DNA methylation) by using a late fusion strategy and machine learning techniques. We train an independent machine learning model for each modality and we explore the interactions and gains that can be obtained by fusing their outputs in an increasing manner, by using a novel optimization approach to compute the parameters of the late fusion. The final classification model, using all modalities, obtains an F1 score of 96.81 +/- 1.07, an AUC of 0.993 +/- 0.004, and an AUPRC of 0.980 +/- 0.016, improving those results that each independent model obtains and those presented in the literature for this problem. These obtained results show that leveraging the multi-scale and multi-omic nature of cancer data can enhance the performance of single-modality clinical decision support systems in personalized medicine, consequently improving the diagnosis of the patient., Government of Andalusia RTI2018-101674-B-I00, CV20-64934 P20-00163

To determine the visual 50:50% perceptibility and acceptability CIEDE2000 lightness, chroma and hue human gingiva thresholds. A psychophysical experiment based on visual assessments of simulated images of human gingiva on a calibrated display was performed. A 20-obsever panel (dentists and laypersons; n=10) evaluated three subsets of simulated human gingiva: lightness subset (|ΔL'/ΔE00|≥ 0.98); chroma subset (|ΔC'/ΔE00|≥ 0.98) and hue subset (|ΔH'/ΔE00|≥ 0.96) using ΔE00 The 50:50% PT were ΔL' = 0.74 (95% confidence interval (CI) 0.39-1.09); ΔC' = 1.10 (95% CI 0.57-1.46); ΔH' = 2.40 (95% CI 1.66->3.85). The 50:50% AT were ΔL' = 2.57 (95% CI 2.00-3.06); ΔC' = 2.70 (95% CI 2.19-3.38). AT ΔH' may be considered no computable. PT values were statistically significant among the three metric differences (p ≤ 0.05). No difference was found between observers for PT values. Statistically differences in perceptual limit were found among hue, lightness and chroma for human gingiva. Thus, the observers seem to show lower sensitivity for changes in hue (ΔH') than in chroma (ΔC') and in lightness (ΔL') in the gingiva color space. PT and AT for lightness, chroma and hue specific for human gingiva should be used when evaluating natural gingiva, pink gingival shade guides or pink materials, since the thresholds of perception and acceptability for teeth are not suitable.

In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify a tumor’s metastatic potential at an early stage. While recent analyses indicated TP53 mutations as candidate biomarker, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in Whole Slide Images (WSIs) offer the potential to mitigate this issue. To assess the potential of WSIs as proxy for spatially resolved profiling or as biomarker for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. On an independent multi-focal cohort, we could show successful generalization of the model, both at patient and lesion level. Hence, the model offers insight into which lesions on a WSI most likely contain a TP53 mutation. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions. This suggests that some FP carry another alteration of which the effect converges in the same histological phenotype. Comparative expression analysis and histological cell type analysis identified such common phenotype (related to stromal composition) in both TP and FP predictions. This indicates that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations. However, we show they have the potential of capturing a tumor’s aggressive potential by observing a downstream phenotype of the tumor cells and TME associated with a biomarker of aggressive disease (TP53). Citation Format: Marija Pizurica, Maarten Larmuseau, Kim Van der Eecken, Louise de Schaetzen van Brienen, Francisco Carrillo-Perez, Simon Isphording, Nicolaas Lumen, Jo Van Dorpe, Piet Ost, Sofie Verbeke, Olivier Gevaert, Kathleen Marchal. WSI based prediction of TP53 mutations identifies aggressive disease phenotype in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB171.

Intra-tumoral heterogeneity and cell-state plasticity are key drivers for the therapeutic resistance of glioblastoma (GBM). Studies based on single-cell RNA-seq and spatial transcriptomics have classified GBM cells into distinct transcriptional phenotypes. However, how the transcriptional diversity and spatial cellular organization are associated with patient prognosis remains incompletely resolved. Here, we developed a deep learning model to predict spatially resolved transcriptional programs from histology images. The model was trained on spatial transcriptomics data and validated in external testing cohorts. Applying the model to two separate patient cohorts led to the discovery of conserved relationships between tumor architecture and prognosis. Patient with poor prognosis had higher proportions of GBM cells expressing a hypoxia-induced transcriptional program. In addition, high clustering patterns of reactive astrocytes were associated with a poor prognosis. Conversely, when the reactive astrocytes were dispersed and connected to other cell types, the risk was decreased. To validate our results, we developed a separate deep learning model that used histology images to predict prognosis. Applying the model to spatial transcriptomics data discovered survival-associated regional gene expression programs. Genes related to glycoprotein metabolism and injury response were significantly upregulated in tumor cells with high aggressiveness. Our studies established a scalable approach to resolve the transcriptional heterogeneity of GBM and linked the spatial cellular architecture to clinical outcomes. Citation Format: Yuanning Zheng, Francisco Carrillo-Perez, Marija Pizurica, Olivier Gevaert. Spatial cellular architecture predicts prognosis in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB272.

Expulsion of incandescent pyroclasts of >64 mm from active volcanoes are known as ‘volcanic bombs’1-3, which can pose significant hazards to life and manmade structures. Most volcanic bombs are considered to fall ballistically, enabling the prediction of a volcanic hazard radius4,5. Here we describe a bomb type that was ejected ballistically, but subsequently travelled downslope a steep volcanic flank, posing an important but hitherto unrecognized impact and fire hazard. The volcanic bombs were observed to fall from the summit of the newly formed La Palma cone in late October 2021 and fell on a soft tephra substrate, travelling downhill for over a kilometer in some instances. The bombs spalled incandescent lava fragments en route, creating a significant fire hazard far beyond the range of ballistic transport. Spallation bomb hazards ought to be considered in volcanic risk assessment, necessitating an increase of hazard radius exceeding a factor of two on steep-sided volcanoes with ballistic bomb activity.

The 2021 eruption of La Palma (September 19-December 13) was the first subaerial eruption in the Canary Islands in 50 years. Approximately 0.2 km3 of lava erupted from a newly formed, broadly basaltic composite volcanic edifice on the northwestern flank of the Cumbre Vieja volcanic ridge. Comprehensive sampling of the olivine-and clinopyroxene-phyric lavas over the eruption period reveals temporal changes in mineralogy and bulk rock geochemistry from tephrite to basanite. Initial tephrite lavas have low MgO (-6 wt.%) and elevated TiO2 (-4 wt.%) and contain amphibole crystals and gabbroic micro -xenoliths. In contrast, lavas with progressively more mafic compositions erupted to approximately day 20 of the eruption and thereafter remained as basanite (-8 wt.% MgO; 3.7 wt.% TiO2) until eruption termination. Temporal changes in lava chemistry reflect initial eruption of fractionated magmas that crystallized 5-10% olivine and clinopyroxene, as well as minor spinel, sulfide, and magnetite, followed by later eruption of deeper-sourced and more primitive magma. Vanadium-in-olivine oxybarometry indicates parental magmas were oxidized (fO2 = +1.5 to +2 FMQ) with 8.2 +/- 0.8 wt.% MgO and were generated from between 2.5-3% partial melting of a mantle source potentially containing a pyroxenite component (Xpx = 0.31 +/- 0.12). Day 1-20 tephrites have more radiogenic 187Os/188Os (0.143-0.148) and lower Pd, Pt, Ir and Os contents than post day 20 basanites (187Os/188Os = 0.141-0.145). Combined with available seismic data, the lavas provide a high-resolution record of eruptive evolution. Initial fractionated tephrite magma was stored in the upper lithosphere up to four years prior to eruption, consistent with pre-cursor seismicity and the presence of partially reacted amphibole and micro-xenoliths. The later lavas of the eruption were fed by more primitive basanitic parental magmas that were likely sourced from the deeper portion of the magma storage system that is underplating the island. Precursor events to the 2021 La Palma eruption involved seismicity and magma emplacement, storage and differentiation, which was followed by mobilisation, eruption, and eventual exhaustion of stored magma and partial melts. This magmatic progression is similar to that documented from the 1949 and 1971 Cumbre Vieja eruptions. Ocean islands with limited basaltic magma supply show similarities to the magmatic evolution observed in large silicic systems, where initial magma emplacement and differentiation is followed by later magma remobilisation that induces volcanic activity.