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Abstract Purpose Loddo et al. (Br J Cancer 100:959–70, 2009) established the prognostic significance of cell cycle markers and "Cell-Cycle Phenotypes" in breast carcinoma. This study aims to 1) identify prognostic cell-cycle markers in sarcoma, and 2) assess the prognostic potential of specific cell-cycle phenotypes in sarcoma. Methods Tissue samples from 128 soft tissue sarcomas were stained for four cell cycle-specific markers: Mcm2, Geminin, Plk1, and H3S10ph. Only primary soft tissue tumors (liposarcoma, leiomyosarcoma, synovial sarcoma, and undifferentiated pleomorphic sarcoma) were included in the analysis. Any tumor coming from a recurrent or metastatic lesion were excluded from the analysis. Three cell-cycle phenotypes (I, II, III) were derived from marker expression patterns. Prognostic significance was evaluated in a subset of primary soft tissue sarcomas using Cox regression for survival analysis. Results Compared to phenotype I, the phenotype III tumors had a decreased 5-year overall survival (HR 6.81 [2.36–19.61]; p =

Tissue-engineered nerve guidance conduits (NGCs) are an area of research interest and investment. Currently, two separate three-dimensional, filled NGCs have Food and Drug Administration approval in the management of nerve gaps up to 3 cm in length, with more on the horizon. Future NGC options will leverage increasingly intricate designs to mimic the natural biology and architecture of native nerve tissue. To enhance the development of next-generation NGCs, experimental protocols and models should be standardized. For the NGCs currently on the market, more clinical data and randomized comparative studies are needed.

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm3 in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients.

Abstract Wind power supply chains are evolving as markets expand to reach climate goals. With the largest installed wind power capacity globally, China must deal with increasing composite turbine waste and anticipate its associated costs. Here we predict the quantity and composition of wind turbine blade waste based on historic deployment. A high-resolution database containing 14 turbine capacities (150–5500 kilowatts) was compiled based on 104 turbine models. The environmental and financial costs of waste treatment options were evaluated using a bottom-up approach. Based on current installations and future projections, 7.7 to 23.1 million tonnes of blade waste will be generated in China by 2050. Technologies exist to recycle glass fibre from blade waste, but these solutions vary in level of maturity and are not always commercially available, cost-competitive, or environmentally sustainable. Our findings can inform decision-makers in governments and industry on the pathways to carbon neutrality.

Cyclonic vortices that are weaker than tropical storm category can bring heavy precipitation as they propagate across the South China Sea and surrounding countries. Here we investigate the structure and dynamics responsible for the intensification of a Borneo vortex that moved from the north of Borneo across the South China Sea and impacted Vietnam and Thailand in late October 2018. This case study is examined using Met Office Unified Model (MetUM) simulations and a semi-geotriptic (SGT) balance approximation tool. Satellite observations and a MetUM simulation with 4.4 km grid initialised at 12:00 UTC on 21 October 2018 show that the westward-moving vortex is characterised by a coherent maximum in total column water and by a comma-shaped precipitation structure with the heaviest rainfall to the northwest of the circulation centre. The Borneo vortex comprises a low-level cyclonic circulation and a mid-level wave embedded in the background easterly shear flow, which strengthens with height up to around 7 km. Despite being in the tropics at 6∘ N, the low-level vortex and mid-level wave are well represented by SGT balance dynamics. The mid-level wave propagates along a vertical gradient in moist stability, i.e. the product between the specific humidity and the static stability, at 4.5 to 5 km and is characterised by a coherent signature in the potential vorticity, meridional wind, and balanced vertical velocity fields. The vertical motion is dominated by coupling with diabatic heating and is shifted relative to the potential vorticity so that the diabatic wave propagates westwards, relative to the flow, at a rate consistent with prediction from moist semi-geostrophic theory. Initial vortex development at low levels is consistent with baroclinic growth initiated by the mid-level diabatic Rossby wave, which propagates on baroclinic shear flow on the southern flank of a large-scale cold surge.

Introducción. Melanoma es un cáncer de piel de mortalidad alta, cuya incidencia ha aumentado mundialmente en los últimos años. El siguiente estudio está destinado a detectar el conocimiento de la población sobre melanoma y las medidas de protección frente a la radiación UV (RUV), considerando que las dos terceras partes de los casos de melanoma se asocian al sol. Objetivo general. Detectar el conocimiento sobre melanoma y las prácticas de protección solar, en pacientes que consultan en el Servicio de Dermatología e internados en Clínica Médica del Hospital José M. Cullen. Materiales y métodos. Estudio observacional, prospectivo, longitudinal y descriptivo. La población abarcó 275 pacientes, entre 16 y 85 años, voluntarios del consultorio de Dermatología e internados en Clínica Médica del Hospital José M. Cullen. Mediante el programa Statistical Package for the Social Sciences 15.0, se realizó un análisis descriptivo y la prueba de Chi cuadrado, para determinar asociación estadística, entre variables cualitativas con significancia de pBackground. Melanoma is one of the deadliest forms of skin cancer, showing an increasing incidence worldwide over the past years. The aim of this study was to assess people's knowledge about melanoma, and their protective measures against UV radiation, considering that two-thirds of melanoma cases are associated to sun exposure. General objective. To assess the knowledge about melanoma and the sun protective practices in patients who attended the Department of Dermatology and in those admitted to the General Internal Medicine Unit of José M. Cullen Hospital. Material and methods. It was an observational, prospective, longitudinal, descriptive study. A sample of 275 participants aged between 16-85 years was included, composed of voluntary patients from the Department of Dermatology and inpatients from the General Internal Medicine Unit of José M. Cullen Hospital. The Statistical Package for the Social Sciences 15.0 software was used to make a descriptive analysis; the chi-square test was performed with a significance level of p < 0.05 to determine the statistical association among qualitative variables. Results. The knowledge was poor, since only 53% of respondents associated melanoma to skin cancer correctly. Hats were the most used sun protection choice, specially in men (p < 0.001). The use of sunscreen was more common among women (p= 0.003) - in fact, they were the ones who used it more regularly (p= 0.011) last summer - and among people under 40 (p= 0.002). Using long clothing was more common in men (p= 0.006) and in people over 40 (p= 0.002). A significant result was found between the use of SPF and its daily reapplication (p < 0.001), between not using any sun protection element and considering that a mole can develop skin cancer (p= 0.014). Conclusion. There is little knowledge among people, which is reflected on the inadequate protective practices against UV radiation.

Abstract Background Monte Carlo (MC) simulations are used in nuclear medicine imaging as they provide unparalleled insight into processes that are not directly experimentally measurable, such as scatter and attenuation in an acquisition. Whilst MC is often used to provide a ‘ground-truth’, this is only the case if the simulation is fully validated against experimental data. This work presents a quantitative validation for a MC simulation of a single-photon emission computed tomography (SPECT) system. Methods An MC simulation model of the Mediso AnyScan SCP SPECT system installed at the UK National Physical Laboratory was developed in the GATE (Geant4 Application for Tomographic Emission) toolkit. Components of the detector head and two collimator configurations were modelled according to technical specifications and physical measurements. Experimental detection efficiency measurements were collected for a range of energies, permitting an energy-dependent intrinsic camera efficiency correction function to be determined and applied to the simulation on an event-by-event basis. Experimental data were collected in a range of geometries with $$^{99\text {m}}$$ 99 m Tc for comparison to simulation. The procedure was then repeated with $$^{177}$$ 177 Lu to determine how the validation extended to another isotope and set of collimators. Results The simulation’s spatial resolution, sensitivity, energy spectra and the projection images were compared with experimental measurements. The simulation and experimental uncertainties were determined and propagated to all calculations, permitting the quantitative agreement between simulated and experimental SPECT acquisitions to be determined. Statistical agreement was seen in sinograms and projection images of both $$^{99\text {m}}$$ 99 m Tc and $$^{177}$$ 177 Lu data. Average simulated and experimental sensitivity ratios of ( $$0.991 \pm 0.011$$ 0.991 ± 0.011 ) were seen for emission and scatter windows of $$^{99\text {m}}$$ 99 m Tc, and ( $$0.897 \pm 0.014$$ 0.897 ± 0.014 ) and ( $$0.839 \pm 0.014$$ 0.839 ± 0.014 ) for the 113 and 208 keV emissions of $$^{177}$$ 177 Lu, respectively. Conclusions MC simulations will always be an approximation of a physical system and the level of agreement should be assessed. A validation method is presented to quantify the level of agreement between a simulation model and a physical SPECT system.

BackgroundGallbladder disease in people is frequently associated with disorders of lipid metabolism and metabolic syndrome. A recently emergent gallbladder disease of dogs, referred to as mucocele formation, is characterized by secretion of abnormal mucus by the gallbladder epithelium and is similarly associated with hyperlipidemia, endocrinopathy, and metabolic dysfunction. The cause of gallbladder mucocele formation in dogs is unknown.MethodsA prospective case-controlled study was conducted to gain insight into disease pathogenesis by characterization of plasma lipid abnormalities in 18 dogs with gallbladder mucocele formation and 18 age and breed matched control dogs using direct infusion mass spectrometry for complex plasma lipid analysis. This analysis was complemented by histochemical and ultrastructural examination of gallbladder mucosa from dogs with gallbladder mucocele formation and control dogs for evidence of altered lipid homeostasis of the gallbladder epithelium.ResultsGallbladder mucocele formation in dogs carried a unique lipidomic signature of increased lipogenesis impacting 50% of lipid classes, 36% of esterified fatty acid species, and 11% of complex lipid species. Broad enrichment of complex lipids with palmitoleic acid (16:1) and decreased abundance within complex lipids of presumptive omega-3 fatty acids eicosapentaenoic (20:5) and docosahexaenoic (22:6) was significant. Severe lipidosis of gallbladder epithelium pinpoints the gallbladder as involved causally or consequently in abnormal lipid metabolism.ConclusionOur study supports a primary increase in lipogenesis in dogs with mucocele formation and abnormal gallbladder lipid metabolism in disease pathogenesis.

Purpose. Recently, the association between ATRX and a more aggressive sarcoma phenotype has been shown. We performed a retrospective study of sarcomas from an individual institution to evaluate ATRX as a prognosticator in soft tissue sarcoma. Experimental Design. 128 sarcomas were collected from a single institution and stained for ATRX. The prognostic significance of these markers was evaluated in a smaller cohort of primary soft tissue sarcomas (n = 68). Kaplan–Meier curves were created for univariate analysis, and Cox regression was utilized for multivariate analysis. Results. High expression of ATRX was found to be a positive prognostic indicator for overall survival and metastasis-free survival in our group of soft tissue sarcomas both in univariate analysis and multivariate analysis (HR: 0.38 (0.17–0.85), P=0.02 and HR: 0.49 (0.24–0.99), P=0.05, respectively). Conclusions. High expression of ATRX is a positive prognostic indicator of overall survival and metastasis-free survival in patients with STS. This is consistent with studies in osteosarcoma, which indicate possible mechanisms through which loss of ATRX leads to more aggressive phenotypes. Future prospective clinical studies are required to validate the prognostic significance of these findings.

Case summary A 10-year-old domestic shorthair cat presented for lethargy, anorexia and labored breathing. Significant pleural and pericardial effusions prompted thoracocentesis and pericardiocentesis. Cytologic evaluation of the pericardial effusion revealed a highly cellular hemorrhagic, eosinophilic (12%) effusion, with many markedly atypical suspected mesothelial cells, interpreted as concerning for neoplasia. Thoracoscopic subtotal pericardiectomy and histology of the pericardium revealed predominantly eosinophilic inflammation with multifocal mesothelial hypertrophy and ulceration. A peripheral eosinophilia was not present on serial complete blood counts. Initial infectious disease testing was mostly negative. Toxoplasma gondii titers were most consistent with prior exposure, although reactivation could not be excluded. The owner’s medical history included a prior diagnosis of bartonellosis. Owing to the challenges of definitive Bartonella species exclusion, the cat was treated empirically with pradofloxacin and doxycycline, and a subtotal pericardectomy. There was improvement at first but pleural effusion recurred approximately 3 months after discharge. The cat was euthanized and a necropsy was not performed. Subsequent pericardial effusion Piroplasma/Bartonella/Borrelia droplet digital PCR detected DNA of Bartonella vinsonii subspecies berkhoffii , and peripheral blood culture and sequencing revealed a rare apicomplexan organism (90% homology with Colpodella species) of unknown clinical significance. Testing for filamentous bacteria and fungal pathogens was not performed. Relevance and novel information This case offers several unique entities – eosinophilic pericardial effusion and eosinophilic pericarditis of unknown etiology – and illustrates the well-known marked atypia that may occur in reactive and hyperplastic mesothelial cells, particularly of infrequently sampled and cytologically described feline pericardial effusion, supporting a cautious interpretation of this cytology finding.

Immune correlates of hepatitis C virus (HCV) clearance and control remain poorly defined due to the lack of an informative animal model. We recently described acute and chronic rodent HCV-like virus (RHV) infections in lab mice. Here, we developed MHC class I and class II tetramers to characterize the serial changes in RHV-specific CD8 and CD4 T cells during acute and chronic infection in C57BL/6J mice. RHV infection induced rapid expansion of T cells targeting viral structural and nonstructural proteins. After virus clearance, the virus-specific T cells transitioned from effectors to long-lived liver-resident memory T cells (TRM). The effector and memory CD8 and CD4 T cells primarily produced Th1 cytokines, IFN-γ, TNF-α, and IL-2, upon ex vivo antigen stimulation, and their phenotype and transcriptome differed significantly between the liver and spleen. Rapid clearance of RHV reinfection coincided with the proliferation of virus-specific CD8 TRM cells in the liver. Chronic RHV infection was associated with the exhaustion of CD8 T cells (Tex) and the development of severe liver diseases. Interestingly, the virus-specific CD8 Tex cells continued proliferation in the liver despite the persistent high-titer viremia and retained partial antiviral functions, as evident from their ability to degranulate and produce IFN-γ upon ex vivo antigen stimulation. Thus, RHV infection in mice provides a unique model to study the function and fate of liver-resident T cells during acute and chronic hepatotropic infection.

Abstract There is a contemporary trend in many major research institutions to de‐emphasize the importance of natural history education in favor of theoretical, laboratory, or simulation‐based research programs. This may take the form of removing biodiversity and field courses from the curriculum and the sometimes subtle maligning of natural history research as a “lesser” branch of science. Additional threats include massive funding cuts to natural history museums and the maintenance of their collections, the extirpation of taxonomists across disciplines, and a critical under‐appreciation of the role that natural history data (and other forms of observational data, including Indigenous knowledge) play in the scientific process. In this paper, we demonstrate that natural history knowledge is integral to any competitive science program through a comprehensive review of the ways in which they continue to shape modern theory and the public perception of science. We do so by reviewing how natural history research has guided the disciplines of ecology, evolution, and conservation and how natural history data are crucial for effective education programs and public policy. We underscore these insights with contemporary case studies, including: how understanding the dynamics of evolutionary radiation relies on natural history data; methods for extracting novel data from museum specimens; insights provided by multi‐decade natural history programs; and how natural history is the most logical venue for creating an informed and scientifically literate society. We conclude with recommendations aimed at students, university faculty, and administrators for integrating and supporting natural history in their mandates. Fundamentally, we are all interested in understanding the natural world, but we can often fall into the habit of abstracting our research away from its natural contexts and complexities. Doing so risks losing sight of entire vistas of new questions and insights in favor of an over‐emphasis on simulated or overly controlled studies.

Hepatitis E virus (HEV) causes self-limited acute hepatitis in immunocompetent individuals and can establish chronic infection in solid organ transplant recipients taking immunosuppressive drugs. A well characterized small animal model is needed to understand HEV pathogenesis. In this study, we established a robust model to study acute and persistent HEV infection using Mongolian gerbils (Meriones unguiculatus) with or without immunosuppression. Gerbils were implanted subcutaneously with continuous release tacrolimus pellet to induce immunosuppression. Gerbils with or without tacrolimus treatment were inoculated with HEV intraperitoneally. Viremia, fecal virus shedding, serum antibody and ALT levels, liver histopathological lesions, hepatocyte apoptosis, and liver macrophage distribution were assessed. Mild to moderate self-limited hepatitis and IgM and IgG antibody responses against HEV ORF2 were observed in immunocompetent gerbils. Levels of HEV-specific IgM responses were higher and lasted longer in immunocompetent gerbils with higher peak viremia. Persistent viremia and fecal virus shedding with either weak, or absent HEV antibody levels were seen in immunosuppressed gerbils. Following HEV infection, serum ALT levels were increased, with lower and delayed peaks observed in immunosuppressed compared to immunocompetent gerbils. In immunocompetent gerbils, foci of apoptotic hepatocytes were detected that were distributed with inflammatory infiltrates containing CD68+ macrophages. However, these foci were absent in immunosuppressed gerbils. The immunosuppressed gerbils showed no inflammation with no increase in CD68+ macrophages despite high virus replication in liver. Our findings suggest adaptive immune responses are necessary for inducing hepatocyte apoptosis, CD68+ macrophage recruitment, and inflammatory cell infiltration in response to HEV infection. Our studies show that Mongolian gerbils provide a promising model to study pathogenesis during acute and persistent HEV infection.

We are grateful to the authors for providing additional data to demonstrate the presence of domestic cat hepadnavirus in lymphoma tissues [...]