CD117 expression in canine ovarian tumours.

Canine ovarian cancer poses a significant diagnostic and therapeutic challenge. The heterogeneous nature of ovarian tumours makes accurate histological identification difficult, whilst treatment is limited to surgical excision. The tyrosine kinase receptor CD117 is neo-expressed in many tumours and represents a potential diagnostic and prognostic biomarker and therapeutic target. This study aimed to establish if CD117 is neoexpressed in canine ovarian tumours. Immunohistochemistry was employed to assess expression of CD117 in 29 canine ovarian tumour samples. CD117 labelling was assessed with a semiquantitative immunoreactivity score, and the location of labelling was recorded as membranous, focal cytoplasmic or diffuse cytoplasmic. Histological morphology was assessed and used to assign subgroups based on growth pattern. Cytokeratin 7 labelling was used to indicate the tumour type as epithelial or sex-cord stromal in origin. Mitotic index, percentage of necrosis and vascular invasion were also assessed and evaluated for association with CD117 expression. Overall, 81% of ovarian tumours neoexpressed CD117 and normal ovarian tissue did not express CD117. Positive immunolabelling was seen in a subset of cells in both ovarian carcinomas (n = 20) and ovarian granulosa cell tumours (n = 3). There was no association between CD117 expression and patient age, histological subtype, mitotic index, percentage of necrosis or vascular invasion. This is the largest study to identify the expression of CD117 in canine ovarian tumours, but further research is needed to elucidate its prognostic and therapeutic value.

Comparison of parent-reported motivators of non-vaccination for children 5-11 years old in Australia and Canada: Results of the iCARE study.

BACKGROUND: Despite COVID-19 infection being less severe in children compared to adults, vaccination for children from the age of 6 months onwards is recommended in many countries to reduce symptom severity and prevent severe disease. However, vaccination against COVID-19 for children remains controversial and uptake has been low. AIMS: To assess and compare the rate of change of parent-reported COVID-19 vaccine uptake in children aged 5 to 11 years and motivators of vaccine acceptance and non-vaccination among parents/guardians in Canada and Australia. METHODS: As part of the iCARE study, two cross-sectional representative samples in Canada and Australia were collected between May 20 and September 12, 2022 (i.e., 5 and 9 months after the COVID-19 vaccine rollout for children 5-11 years) using online panels. Parents/guardians reported the vaccine status of their children and motivators for vaccine acceptance and non-vaccination. General linear models were used to estimate differences between countries in terms of vaccine uptake and motivators across time. RESULTS: Parent-reported vaccine uptake for children 5-11 years didn't increase over the study period (T1 = 87 %,T2 = 86 %; OR = 0.83; 95 %CI = 0.45-1.54) and was overall lower in Canada (60.8 %) compared to Australia (71.6 %)(OR = 0.56; 95 %CI = 0.33-0.96). In both countries the socioeconomic characteristics of parents who didn't vaccinate their children were similar and having information on either the short- or long-term side effects of the vaccine were important motivators. However, vaccine effectiveness was more important in Canada and trust in the company that developed the vaccine and a recommendation from the child's doctor were more important motivators in Australia. CONCLUSION: Parent-reported vaccine uptake for children 5-11 years plateaued early in the vaccine rollout. The main motivators for parents of unvaccinated children varied between the two countries but information on vaccine safety and effectiveness were common to both countries. Findings may inform future tailored vaccine communication efforts and pandemic planning in Australia and Canada to optimize vaccine uptake for primary school children.

From Pixels to Prognosis: Unlocking the Potential of Deep Learning in Fibrotic Lung Disease Imaging Analysis.

The licensing of antifibrotic therapy for fibrotic lung diseases, including idiopathic pulmonary fibrosis IPF has created an urgent need for reliable biomarkers to predict disease progression and treatment response. Some patients experience stable disease trajectories, while others deteriorate rapidly, making treatment decisions challenging. High-resolution chest CT has become crucial for diagnosis, but visual assessments by radiologists suffer from low reproducibility and high interobserver variability. To address these issues, computer-based image analysis, called quantitative CT, has emerged. However, many quantitative CT methods rely on human input for training, therefore potentially incorporating human error into computer training. Rapid advances in artificial intelligence, specifically deep learning, aim to overcome this limitation by enabling autonomous quantitative analysis. While promising, deep learning also presents challenges including the need to minimize algorithm biases, ensuring explainability, and addressing accessibility and ethical concerns. This review explores the development and application of deep learning in improving the imaging process for fibrotic lung disease.

Intra-operative extracorporeal irradiation of tumour-invaded craniotomy bone flap in meningioma: a case series.

BACKGROUND: Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC. METHODS: Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected. RESULTS: Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded. CONCLUSION: EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies.

References for Small Fluorescence Quantum Yields.

Three compounds with fluorescence quantum yields in the range of 10- 5 to 10- 4 and emission spectra covering the UV/Vis spectral range are suggested as new references for the determination of small fluorescence quantum yields. The compounds are thymidine (dT) in water, dibenzoylmethane (DBM) in ethanol, and malachite green chloride (MG) in water, representing the blue, green, and red regions of the spectrum, respectively. All compounds are easily handled, photostable, and commercially available. Furthermore, these compounds exhibit a mirror-image symmetry between their absorption and fluorescence spectra. This symmetry, along with closely aligned fluorescence excitation and absorption spectra, confirms that the observed emissions originate from the compounds themselves. The fluorescence quantum yields were determined via a relative approach as well as Strickler-Berg analysis in conjunction with time resolved fluorescence spectroscopy. Within the respective error margins, the two approaches yielded identical results.

Growth-induced collective bending and kinetic trapping of cytoskeletal filaments.

Growth and turnover of actin filaments play a crucial role in the construction and maintenance of actin networks within cells. Actin filament growth occurs within limited space and finite subunit resources in the actin cortex. To understand how filament growth shapes the emergent architecture of actin networks, we developed a minimal agent-based model coupling filament mechanics and growth in a limiting subunit pool. We find that rapid filament growth induces kinetic trapping of highly bent actin filaments. Such collective bending patterns are long-lived, organized around nematic defects, and arise from competition between filament polymerization and bending elasticity. The stability of nematic defects and the extent of kinetic trapping are amplified by an increase in the abundance of the actin pool and by crosslinking the network. These findings suggest that kinetic trapping is a robust consequence of growth in crowded environments, providing a route to program shape memory in actin networks.

Dietary fibre supplementation enhances radiotherapy tumour control and alleviates intestinal radiation toxicity.

BACKGROUND: Non-toxic approaches to enhance radiotherapy outcomes are beneficial, particularly in ageing populations. Based on preclinical findings showing that high-fibre diets sensitised bladder tumours to irradiation by modifying the gut microbiota, along with clinical evidence of prebiotics enhancing anti-cancer immunity, we hypothesised that dietary fibre and its gut microbiota modification can radiosensitise tumours via secretion of metabolites and/or immunomodulation. We investigated the efficacy of high-fibre diets combined with irradiation in immunoproficient C57BL/6 mice bearing bladder cancer flank allografts. RESULT: Psyllium plus inulin significantly decreased tumour size and delayed tumour growth following irradiation compared to 0.2% cellulose and raised intratumoural CD8+ cells. Post-irradiation, tumour control positively correlated with Lachnospiraceae family abundance. Psyllium plus resistant starch radiosensitised the tumours, positively correlating with Bacteroides genus abundance and increased caecal isoferulic acid levels, associated with a favourable response in terms of tumour control. Psyllium plus inulin mitigated the acute radiation injury caused by 14 Gy. Psyllium plus inulin increased caecal acetate, butyrate and propionate levels, and psyllium alone and psyllium plus resistant starch increased acetate levels. Human gut microbiota profiles at the phylum level were generally more like mouse 0.2% cellulose profiles than high fibre profiles. CONCLUSION: These supplements may be useful in combination with radiotherapy in patients with pelvic malignancy. Video Abstract.

Electrocatalytic Formal C(sp2)-H Alkylations via Nickel-Catalyzed Cross-Electrophile Coupling with Versatile Arylsulfonium Salts.

Producing sp3-hybridized carbon-enriched molecules is of particular interest due to their high success rate in clinical trials. The installation of aliphatic chains onto aromatic scaffolds was accomplished by nickel-catalyzed C(sp2)-C(sp3) cross-electrophile coupling with arylsulfonium salts. Thus, simple non-prefunctionalized arenes could be alkylated through the formation of aryldibenzothiophenium salts. The reaction employs an electrochemical approach to avoid potentially hazardous chemical redox agents, and importantly, the one-pot alkylation proved also viable, highlighting the robustness of our approach.

Rural healthcare workforce preparation, response, and work during the COVID-19 pandemic in Australia: Lessons learned from in-depth interviews with rural health service leaders.

BACKGROUND: Low population density, geographic spread, limited infrastructure and higher costs are unique challenges in the delivery of healthcare in rural areas. During the COVID-19 pandemic, emergency powers adopted globally to slow the spread of transmission of the virus included population-wide lockdowns and restrictions upon movement, testing, contact tracing and vaccination programs. The aim of this research was to document the experiences of rural health service leaders as they prepared for the emergency pandemic response, and to derive from this the lessons learned for workforce preparedness to inform recommendations for future policy and emergency planning. METHODOLOGY AND METHODS: Interviews were conducted with leaders from two rural public health services in Australia, one small (500 staff) and one large (3000 staff). Data were inductively coded and analysed thematically. PARTICIPANTS: Thirty-three participants included health service leaders in executive, clinical, and administrative roles. FINDINGS: Six major themes were identified: Working towards a common goal, Delivery of care, Education and training, Organizational governance and leadership, Personal and psychological impacts, and Working with the Local Community. Findings informed the development of a applied framework. CONCLUSION: The study findings emphasise the critical importance of leadership, teamwork and community engagement in preparing the emergency pandemic response in rural areas. Informed by this research, recommendations were made to guide future rural pandemic emergency responses or health crises around the world.

Influence of the substitution position on spin communication in photoexcited perylene-nitroxide dyads.

By virtue of the modularity of their structures, their tunable optical and magnetic properties, and versatile applications, photogenerated triplet-radical systems provide an ideal platform for the study of the factors controlling spin communication in molecular frameworks. Typically, these compounds consist of an organic chromophore covalently attached to a stable radical. After formation of the chromophore triplet state by photoexcitation, two spin centres are present in the molecule that will interact. The nature of their interaction is governed by the magnitude of the exchange interaction between them and can be studied by making use of transient electron paramagnetic resonance (EPR) techniques. Here, we investigate three perylene-nitroxide dyads that only differ with respect to the position where the nitroxide radical is attached to the perylene core. The comparison of the results from transient UV-vis and EPR experiments reveals major differences in the excited state properties of the three dyads, notably their triplet state formation yield, excited state deactivation kinetics, and spin coherence times. Spectral simulations and quantum chemical calculations are used to rationalise these findings and demonstrate the importance of considering the structural flexibility and the contribution of rotational conformers for an accurate interpretation of the data.

Palmitoyl transferase ZDHHC20 promotes pancreatic cancer metastasis.

Metastasis is one of the defining features of pancreatic ductal adenocarcinoma (PDAC) that contributes to poor prognosis. In this study, the palmitoyl transferase ZDHHC20 was identified in an in vivo short hairpin RNA (shRNA) screen as critical for metastatic outgrowth, with no effect on proliferation and migration in vitro or primary PDAC growth in mice. This phenotype is abrogated in immunocompromised animals and animals with depleted natural killer (NK) cells, indicating that ZDHHC20 affects the interaction of tumor cells and the innate immune system. Using a chemical genetics platform for ZDHHC20-specific substrate profiling, a number of substrates of this enzyme were identified. These results describe a role for palmitoylation in enabling distant metastasis that could not have been detected using in vitro screening approaches and identify potential effectors through which ZDHHC20 promotes metastasis of PDAC.

Building a cm2scale CVD graphene-based gas sensor: modelling the kinetic with a three-site adsorption/desorption Langmuir model.

In this article, we aim to develop and study a highly sensitive and selective cm2scale graphene-based gas sensor. We present the technology used to fabricate sensors which integrate monolayer chemical vapour deposition graphene: photolithography and transfer of layers. Characterization techniques (optical microscopy, AFM, micro-Raman spectroscopy, transport electrical measurements) ensure a diagnosis of graphene ribbons and allow good reproducibility of technological processes. We present the results of gas characterizations after a 200 ppm NO2exposure. We propose a novel approach for the modelling of the sensor response with a three-site adsorption/desorption Langmuir model. This innovative way of modelling the sensor response should provide a better understanding of the sensor's kinetic and help to overcome the long response time observed with graphene gas sensors.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Bayesian workflow for time-varying transmission in stratified compartmental infectious disease transmission models.

Compartmental models that describe infectious disease transmission across subpopulations are central for assessing the impact of non-pharmaceutical interventions, behavioral changes and seasonal effects on the spread of respiratory infections. We present a Bayesian workflow for such models, including four features: (1) an adjustment for incomplete case ascertainment, (2) an adequate sampling distribution of laboratory-confirmed cases, (3) a flexible, time-varying transmission rate, and (4) a stratification by age group. Within the workflow, we benchmarked the performance of various implementations of two of these features (2 and 3). For the second feature, we used SARS-CoV-2 data from the canton of Geneva (Switzerland) and found that a quasi-Poisson distribution is the most suitable sampling distribution for describing the overdispersion in the observed laboratory-confirmed cases. For the third feature, we implemented three methods: Brownian motion, B-splines, and approximate Gaussian processes (aGP). We compared their performance in terms of the number of effective samples per second, and the error and sharpness in estimating the time-varying transmission rate over a selection of ordinary differential equation solvers and tuning parameters, using simulated seroprevalence and laboratory-confirmed case data. Even though all methods could recover the time-varying dynamics in the transmission rate accurately, we found that B-splines perform up to four and ten times faster than Brownian motion and aGPs, respectively. We validated the B-spline model with simulated age-stratified data. We applied this model to 2020 laboratory-confirmed SARS-CoV-2 cases and two seroprevalence studies from the canton of Geneva. This resulted in detailed estimates of the transmission rate over time and the case ascertainment. Our results illustrate the potential of the presented workflow including stratified transmission to estimate age-specific epidemiological parameters. The workflow is freely available in the R package HETTMO, and can be easily adapted and applied to other infectious diseases.

Topography and Ensemble Activity in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.

Autism spectrum disorder (ASD) is often associated with social communication impairments and specific sound processing deficits, for example, problems in following speech in noisy environments. To investigate underlying neuronal processing defects located in the auditory cortex (AC), we performed two-photon Ca2+ imaging in FMR1 (fragile X messenger ribonucleoprotein 1) knock-out (KO) mice, a model for fragile X syndrome (FXS), the most common cause of hereditary ASD in humans. For primary AC (A1) and the anterior auditory field (AAF), topographic frequency representation was less ordered compared with control animals. We additionally analyzed ensemble AC activity in response to various sounds and found subfield-specific differences. In A1, ensemble correlations were lower in general, while in secondary AC (A2), correlations were higher in response to complex sounds, but not to pure tones. Furthermore, sound specificity of ensemble activity was decreased in AAF. Repeating these experiments 1 week later revealed no major differences regarding representational drift. Nevertheless, we found subfield- and genotype-specific changes in ensemble correlation values between the two times points, hinting at alterations in network stability in FMR1 KO mice. These detailed insights into AC network activity and topography in FMR1 KO mice add to the understanding of auditory processing defects in FXS.

A practical guide to EEG hyperscanning in joint action research: from motivation to implementation.

Developments in cognitive neuroscience have led to the emergence of hyperscanning, the simultaneous measurement of brain activity from multiple people. Hyperscanning is useful for investigating social cognition, including joint action, because of its ability to capture neural processes that occur within and between people as they coordinate actions toward a shared goal. Here, we provide a practical guide for researchers considering using hyperscanning to study joint action and seeking to avoid frequently raised concerns from hyperscanning skeptics. We focus specifically on Electroencephalography (EEG) hyperscanning, which is widely available and optimally suited for capturing fine-grained temporal dynamics of action coordination. Our guidelines cover questions that are likely to arise when planning a hyperscanning project, ranging from whether hyperscanning is appropriate for answering one's research questions to considerations for study design, dependent variable selection, data analysis and visualization. By following clear guidelines that facilitate careful consideration of the theoretical implications of research design choices and other methodological decisions, joint action researchers can mitigate interpretability issues and maximize the benefits of hyperscanning paradigms.

Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4+ T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1fl/flMaffl/flCd4Cre mice infected with Helicobacter hepaticus developed severe colitis with an increase in TH1/NK/ILC1 effector genes in LPLs, while Prdm1fl/flCd4Cre and Maffl/flCd4Cre mice exhibited moderate pathology and a less-marked type 1 effector response. LPLs from infected Maffl/flCd4Cre mice had increased type 17 responses with increased Il17a and Il22 expression and an increase in granulocytes and myeloid cell numbers, resulting in increased T cell-myeloid-neutrophil interactions. Genes over-expressed in human inflammatory bowel disease showed differential expression in LPLs from infected mice in the absence of Prdm1 or Maf, revealing potential mechanisms of human disease.

Progressive Pulmonary Fibrosis and Interstitial Lung Abnormalities: AJR Expert Panel Narrative Review.

Progressive pulmonary fibrosis (PPF) and interstitial lung abnormalities (ILA) are relatively new concepts in interstitial lung disease (ILD) imaging and clinical management. Recognition of signs of PPF, as well as identification and classification of ILA, are important tasks during chest high-resolution CT interpretation, to optimize management of patients with ILD and those at risk of developing ILD. However, following professional society guidance, the role of imaging surveillance remains unclear in stable patients with ILD, asymptomatic patients with ILA who are at risk of progression, and asymptomatic patients at risk of developing ILD without imaging abnormalities. In this AJR Expert Panel Narrative Review, we summarize the current knowledge regarding PPF and ILA and describe the range of clinical practice with respect to imaging patients with ILD, those with ILA, and those at risk of developing ILD. In addition, we offer suggestions to help guide surveillance imaging in areas with an absence of published guidelines, where such decisions are currently driven primarily by local pulmonologists' preference.