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ObjectiveDetermine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends.MethodsThe medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions.ResultsOf the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years).ConclusionsThe findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases.Clinical relevanceUnderstanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

Over the past two decades, it has become increasingly apparent that early Mars may once have been warmer, wetter and more habitable for microbial life than it is today, which has spurred discussions about potential biosignatures that may be preserved in Martian sediments. An impediment to this line of research is the pervasive oxidation of Mars’ surface due to photochemical oxidants that have likely destroyed remnants of organic matter. Here, we investigate whether nitrogen (N) transferred from biomass to phyllosilicate minerals during diagenesis can be preserved in oxidized mudrocks. We investigate two sequences of terrestrial Proterozoic red beds, namely the Sibley Group (1.4 Ga) in Canada and the Stoer Group (1.2 Ga) in Scotland, and we find enrichments in authigenic N in the range of several tens of ppm in both units. The highest concentrations (ca. 100 ppm on average) are found in the most desiccated red beds of the Stoer Group, concurrent with enrichments in potassium (K). We discuss similarities and differences between the two sets of rocks with regards to salinity, pH, biological productivity and K-metasomatism, and we conclude that the ideal mechanism for the preservation of biogenic N in red beds may be in-situ release of ammonium from microbial mats into the clay substrate, possibly facilitated by early diagenetic, biologically induced illitization. Illite and smectite have been observed on Mars, and experiments suggest that Martian waters contained moderate amounts of dissolved K. Hence, it is conceivable that a similar K and N enrichment process could have occurred as to what we document for the Proterozoic, preserving evidence of life that may have survived to the modern day.

Abstract Low solubility and low reactivity towards organic compounds make phosphorus a problematic element for the origin and early evolution of life. Reduced and polymerized phosphorus species are more bioavailable and may resolve these issues, but widespread formation pathways for these species are not well understood. Here we show, using experiments and thermodynamic modelling, that diverse polyphosphates (straight-chains with up to five and cyclophosphates with three and four phosphate molecules) and reduced phosphite can form under ferruginous anhydrous conditions at 80-700 °C. We find that hydrogen and temperature enhance phosphite production while polyphosphate formation maximizes at moderate temperatures (175-200 °C). Chromite and Nickel-bearing minerals enhance phosphate polymerization and reduction whereas magnetite inhibits them. These findings expand on previous investigations of thermally induced changes in phosphorus-speciation and show that these reactions may be widespread in nature. Metamorphism of ferruginous sediments, serpentinization, as well as subaerial lakes exposed to volcanic heating could potentially produce a wealth of polyphosphates along with phosphite on the early Earth. Later, these species may have participated in prebiotic phosphorylation reactions upon liberation by subsequent fluid infiltration. Our results thus offer a more widespread pathway for the generation of reactive phosphorus for the origin of life.

Despite the wide usage of screen media among young children, less is known about the relationships between children's screen time and their social competence development as impacted by family-related factors. Here, we investigated parents' engagement, children's screen time, and their social competence among Taiwanese Chinese children's families at three time points as the children aged (Time 1: N = 2,037, including 991 girls, M = 3.00 years; Time 2: N = 1,785, including 868 girls, M = 4.00 years; Time 3: N = 1,749, including 842 girls, M = 5.01 years). "Research Findings": From ages 3 to 5 years, parental engagement positively predicted children's social competence, whereas children's screen time negatively predicted their social competence. Examination of the mechanism underlying these longitudinal relationships suggested that when parents engaged less frequently in interacting with children, their children tended to spend more time on screen media, and then developed a lower level of social competence during the early years. "Practice or Policy": Our findings indicate that young children's time spent on screen media should be monitored and restricted. Instead of keeping children occupied with screen media, parents and educators should engage more actively in interacting with children to promote their social competence.

Abstract Laser-driven compact particle accelerators can provide ultrashort pulses of broadband X-rays, well suited for undertaking X-ray absorption spectroscopy measurements on a femtosecond timescale. Here the Extended X-ray Absorption Fine Structure (EXAFS) features of the K-edge of a copper sample have been observed over a 250 eV window in a single shot using a laser wakefield accelerator, providing information on both the electronic and ionic structure simultaneously. This capability will allow the investigation of ultrafast processes, and in particular, probing high-energy-density matter and physics far-from-equilibrium where the sample refresh rate is slow and shot number is limited. For example, states that replicate the tremendous pressures and temperatures of planetary bodies or the conditions inside nuclear fusion reactions. Using high-power lasers to pump these samples also has the advantage of being inherently synchronised to the laser-driven X-ray probe. A perspective on the additional strengths of a laboratory-based ultrafast X-ray absorption source is presented.

Abstract Phosphorus plays a crucial role in controlling biological productivity, but geological estimates of phosphate concentrations in the Precambrian ocean, during life’s origin and early evolution, vary over several orders of magnitude. While reduced phosphorus species may have served as alternative substrates to phosphate, their bioavailability on the early Earth remains unknown. Here, we reconstruct the phylogenomic record of life on Earth and find that phosphate transporting genes (pnas) evolved in the Paleoarchean (ca. 3.6-3.2 Ga) and are consistent with phosphate concentrations above modern levels ( > 3 µM). The first gene optimized for low phosphate levels (pstS;

Abstract The transformation of biomasses from agro-industrial waste can significantly impact the production of green chemicals from sustainable resources. Pectin is a biopolymer present in lignocellulosic biomass as Orange Peel Waste (OPW) and has possibilities for making platform compounds such as furfural for sustainable chemistry. In this work, we studied the transformation to furfural of OPW, pectins, and d-galacturonic acid (D-GalA), which is the main component (65 wt%) of pectin. We analyzed pectins with different degrees of esterification (45, 60 and 95 DE) in a one-pot hydrolysis reaction system and studied the differences in depolymerization and dehydration of the carbohydrates. The results show that the production of furfural decreases as the DE value increases. Specifically, low DE values favor the formation of furfural since the decarboxylation reaction is favored over deesterification. Interestingly, the furfural concentration is dependent upon the polysaccharide composition of pentoses and uronic acid. The obtained concentrations of furfural (13 and 14 mmol/L), d-xylose (6.2 and 10 mmol/L), and L-arabinose (2.5 and 2.7 mmol/L) remained the same when the galacturonic acid was fed either as a polymer or a monomer under the same reaction conditions (0.01 M SA, 90 min and 433 K). OPW is proposed as a feedstock in a biorefinery, in which on a per kg OPW dry basis, 90 g of pectin and 15 g of furfural were produced in the most favorable case. We conclude that the co-production of pectin and furfural from OPW is economically feasible. Graphical Abstract

Background and purpose: The target structures for cervix brachytherapy are segmented by radiation oncologists using imaging and clinical information. At the first fraction, this is performed manually from scratch. For subsequent fractions the first fraction segmentations are rigidly propagated and edited manually. This process is time-consuming while patients wait immobilized. In this work, we evaluate the potential clinical impact of using population-based and patient-specific auto-segmentations as a starting point for target segmentation of the second fraction. Materials and method: For twenty-eight patients with locally advanced cervical cancer, treated with MRI-guided brachytherapy, auto-segmentations were retrospectively generated for the second fraction image using two approaches: 1) population-based model, 2) patient-specific models fine-tuned on first fraction information. A radiation oncologist manually edited the auto-segmentations to assess model-induced bias. Pairwise geometric and dosimetric comparisons were performed for the automatic, edited and clinical structures. The time spent editing the auto-segmentations was compared to the current clinical workflow. Results: The edited structures were more similar to the automatic than to the clinical structures. The geometric and dosimetric differences between the edited and the clinical structures were comparable to the inter-observer variability investigated in literature. Editing the auto-segmentations was faster than the manual segmentation performed during our clinical workflow. Patient-specific auto-segmentations required less edits than population-based structures. Conclusions: Auto-segmentation introduces a bias in the manual delineations but this bias is clinically irrelevant. Auto-segmentation, particularly patient-specific fine-tuning, is a time-saving tool that can improve treatment logistics and therefore reduce patient burden during the second fraction of cervix brachytherapy.

Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use-inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill-building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and bring death, by causing devastating diseases in humans, plants, and animals. With climate change, increased antimicrobial resistance, global trade, environmental degradation, and novel viruses altering the impact of fungi on health and disease, developing new approaches is now more crucial than ever to combat the threats posed by fungi and to harness their extraordinary potential for applications in human health, food supply, and environmental remediation. To address this aim, the Canadian Institute for Advanced Research (CIFAR) and the Burroughs Wellcome Fund convened a workshop to unite leading experts on fungal biology from academia and industry to strategize innovative solutions to global challenges and fungal threats. This report provides recommendations to accelerate fungal research and highlights the major research advances and ideas discussed at the meeting pertaining to 5 major topics: (1) Connections between fungi and climate change and ways to avert climate catastrophe; (2) Fungal threats to humans and ways to mitigate them; (3) Fungal threats to agriculture and food security and approaches to ensure a robust global food supply; (4) Fungal threats to animals and approaches to avoid species collapse and extinction; and (5) Opportunities presented by the fungal kingdom, including novel medicines and enzymes.

Abstract Carotenoids are hydrophobic pigments binding to diverse carotenoproteins, many of which remain unexplored. Focusing on yellow gregarious locusts accumulating cuticular carotenoids, here we use engineered Escherichia coli cells to reconstitute a functional water-soluble β-carotene-binding protein, BBP. HPLC and Raman spectroscopy confirmed that recombinant BBP avidly binds β-carotene, inducing the unusual vibronic structure of its absorbance spectrum, just like native BBP extracted from the locust cuticles. Bound to recombinant BBP, β-carotene exhibits pronounced circular dichroism and allows BBP to withstand heating (T 0.5 = 68 °C), detergents and pH variations. Using bacteria producing distinct xanthophylls we demonstrate that, while β-carotene is the preferred carotenoid, BBP can also extract from membranes ketocarotenoids and, very poorly, hydroxycarotenoids. We show that BBP-carotenoid complex reversibly binds to chitin, but not to chitosan, implying the role for chitin acetyl groups in cuticular BBP deposition. Reconstructing such locust coloration mechanism in vitro paves the way for structural studies and BBP applications.

Background and objective: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease. Methods: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT. Key findings and limitations: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64–0.79). Using our nomogram, patients with a predicted risk of >20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT. Conclusions: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment. Patient summary: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.

Background The high incidence of knee injuries in football/handball challenges effective prevention. Identifying tangible and modifiable factors associated with a knee injury may innovate preventive actions. Engaging key stakeholders can reveal crucial insights that could improve knee injury prevention in football/handball.Objective To investigate football/handball stakeholders’ perspectives on reasons for acute and severe knee injuries to generate a conceptual model on important factors associated with knee injuries in football/handball.Methods Mixed-method participatory Group Concept Mapping was applied to collect statements from football/handball stakeholders (players/coaches/healthcare staff/researchers) on the question, ‘What may explain why some players sustain a knee injury?’. Participants rated the importance and feasibility of screening for each statement. Multidimensional scaling and hierarchical cluster analysis produced a cluster map, forming the basis for developing a final conceptual model.Results Stakeholders (n=37) generated and sorted 100 statements. Cluster analysis followed by cluster map validation yielded seven themes: (1) the player’s physical and motor skill profile, (2) preparation and training, (3) footwear and playing surface, (4) the sport’s impact on the risk of injury, (5) mental and physical fatigue, (6) history of injury and 7) genetics and context. A final conceptual model illustrating factors associated with knee injuries in football/handball was developed. Forty-six statements were identified as both important and feasible to screen for.Conclusions Stakeholders’ perspectives on knee injuries in football/handball revealed a complex interplay of factors. We developed a conceptual model fostering stakeholder dialogue for enhanced prevention. Key among its themes is ‘preparation and training’.

Estimamos índices de sentimiento a nivel regional y nacional utilizando información en formato de texto del Programa Trimestral de Entrevistas a Directivos, empleada para la elaboración del Reporte sobre las Economías Regionales del Banco de México, referente a los factores que los entrevistados consideran que afectaron, afectan o pudieran afectar la actividad económica en su sector o entidad federativa. Estos índices, estimados con información de los programas de entrevistas trimestrales llevados a cabo entre enero de 2016 y enero de 2021, son posteriormente asociados con diferentes indicadores de actividad económica regional y nacional publicados por el INEGI, obteniéndose correlaciones positivas y estadísticamente significativas entre los índices de sentimiento y algunos indicadores de actividad económica. Dado que estos índices de sentimiento pueden obtenerse con mayor rapidez que la mayoría de los indicadores tradicionales de actividad económica aquí analizados, el trabajo destaca la relevancia de la información en formato de texto contenida en el Programa Trimestral de Entrevistas a Directivos para complementar la obtenida con indicadores tradicionales.

Antecedentes y objetivo: El presente estudio analiza un pseudobrote relacionado con Providencia rettgeri en pacientes sometidos a broncoscopias, identificando factores de riesgo, medidas de control y conclusiones relevantes para la prevención de futuros eventos similares. Material y método: Se revisaron los casos afectados y se evaluaron los procedimientos de broncoscopia utilizados. Se hizo un seguimiento epidemiológico detallado de los pacientes, así como auditorías de control de calidad en las unidades implicadas. Resultados: Se identificaron 13 pacientes con cultivos positivos para P. rettgeri tras someterse a broncoscopias. Ninguno de estos pacientes desarrolló infección clínica, considerándose pseudobrote. Las auditorías de control de infecciones confirmaron la adecuación de los protocolos y medidas de bioseguridad. Conclusiones: Los hallazgos sugieren que la colonización bacteriana previa en un paciente, combinada con el estado defectuoso del broncoscopio, pudo favorecer la formación de biofilm, desencadenando la liberación continuada del microorganismo, subrayando la importancia de revisar los protocolos de control de infecciones y llevar a cabo un mantenimiento riguroso de los dispositivos médicos. Como conclusión se destaca la necesidad de fortalecer los protocolos de control de infecciones, especialmente en casos de colonización bacteriana previa. Es importante una vigilancia continua y revisiones periódicas para garantizar la seguridad de los procedimientos médicos.

Emerging evidence indicates an association between altered immune system functioning, inflammatory response activation, and major depression (MD). This study examined the association between major depression in young people and the monocyte-to-lymphocyte (MLR) and neutrophil-to-lymphocyte ratio (NLR). Inflammation markers were estimated from DNA methylation data using an established cell-mixture deconvolution algorithm and examined in a well-characterized, antidepressant free epidemiological sample of young twins (N = 170). No statistically significant differences were observed between young persons with and without Lifetime MD for the MLR and NLR. A post-hoc analysis of time since last major depressive episode (MDE) indicated that more recent MDEs were associated with higher MLR and NLR levels compared to temporally distant MDEs. A second post-hoc analysis using the full sample determined that past year MDEs were associated with elevated MLR and NLR scores compared to persons unaffected by lifetime MD and person experiencing their last MDE over one year ago. Finally, T cell immunity was most consistently associated with recent MDEs, suggesting that levels of this adaptive immune cell were diminished. Young people experiencing a recent MDE demonstrated increased levels of inflammation with T cells exhibiting the most persistent associations with depression outcomes. Etiological and treatment implications of results are discussed.

Abstract Background Cognitive impairments are prevalent across mood disorders and psychosis spectrum disorders, but there is a lack of real-life-like cognitive training programmes. Fully immersive virtual reality has the potential to ensure motivating and engaging cognitive training directly relevant to patients’ daily lives. We will examine the effect of a 4-week, intensive virtual reality-based cognitive remediation programme involving daily life challenges on cognition and daily life functioning in patients with mood disorders or psychosis spectrum disorders and explore the neuronal underpinnings of potential treatment efficacy. Methods The trial has a randomized, controlled, double-blinded, parallel-group design. We will include 66 symptomatically stable outpatients with mood disorders or psychosis spectrum disorders aged 18–55 years with objective and subjective cognitive impairment. Assessments encompassing a virtual reality test of daily life cognitive skills, neuropsychological testing, measures of daily life functioning, symptom ratings, questionnaires on subjective cognitive complaints, and quality of life are carried out at baseline, after the end of 4 weeks of treatment and at a 3-month follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and at the end of treatment. The primary outcome is a broad cognitive composite score comprising five subtasks on a novel ecologically valid virtual reality test of daily life cognitive functions. Two complete data sets for 54 patients will provide a power of 80% to detect a clinically relevant between-group difference in the primary outcome. Behavioural data will be analysed using linear mixed models in SPSS, while MRI data will be analysed with the FMRIB Expert Analysis Tool (FEAT). Treatment-related changes in neural activity from baseline to end of treatment will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest. Discussion The results will provide insight into whether virtual reality-based cognitive remediation has beneficial effects on cognition and functioning in symptomatically stable patients with mood disorders or psychosis spectrum disorders, which can aid future treatment development. Trial registration ClinicalTrials.gov NCT06038955. Registered on September 15, 2023.