Variability in the reported management of pulmonary metastases in osteosarcoma.

Nearly 20% of patients with newly diagnosed osteosarcoma have detectable metastases at diagnosis; the majority of which occur in the lungs. There are no established recommendations for the timing and modality of metastasectomy. Members of the Connective Tissue Oncology Society (CTOS) were emailed an anonymous 10-min survey assessing their management practices for pulmonary findings at the time of an osteosarcoma diagnosis. The questionnaire presented three scenarios and discussed the choice to perform surgery, the timing of resection, and the choice of surgical procedure. Analyses were stratified by medical profession. One hundred and eighty-three physicians responded to our questionnaire. Respondents were comprised of orthopedic surgeons (37%), medical oncologists (31%), pediatric oncologists (22%), and other medical subspecialties (10%). There was variability among the respondents in the management of the pulmonary nodules. The majority of physicians chose to resect the pulmonary nodules following neoadjuvant chemotherapy (46-63%). Thoracotomy was the preferred technique for surgical resection. When only unilateral findings were present, the majority of physicians did not explore the contralateral lung. The majority of respondents did not recommend resection if the pulmonary nodule disappeared following chemotherapy. The survey demonstrated heterogeneity in the management of pulmonary metastases in osteosarcoma. Prospective trials need to evaluate whether these differences in management have implications for outcomes for patients with metastatic osteosarcoma

Elements of the B Cell Signalosome Are Differentially Affected by Mercury Intoxication

It has been suggested that environmental exposures to mercury contribute to autoimmune disease. Disruption of BCR signaling is associated with failure of central tolerance and autoimmunity, and we have previously shown that low levels of Hg2+ interfere with BCR signaling. In this report we have employed multiparametric phosphoflow cytometry, as well as a novel generalization of the Overton algorithm from one- to two-dimensional unimodal distributions to simultaneously monitor the effect of low level Hg2+ intoxication on activation of ERK and several upstream elements of the BCR signaling pathway in WEHI-231 B cells. We have found that, after exposure to low levels of Hg2+, only about a third of the cells are sensitive to the metal. For those cells which are sensitive, we confirm our earlier work that activation of ERK is attenuated but now report that Hg2+ has little upstream effect on the Btk tyrosine kinase. On the other hand, we find that signaling upstream through the Syk tyrosine kinase is actually augmented, as is upstream activation of the B cell signalosome scaffolding protein BLNK

Red-list status and extinction risk of the world’s whales, dolphins and porpoises

To understand the scope and scale of the loss of biodiversity, tools are required that can be applied in a standardized manner to all species globally, spanning realms from land to the open ocean. We used data from the International Union for the Conservation of Nature Red List to provide a synthesis of the conservation status and extinction risk of cetaceans. One in 4 cetacean species (26% of 92 species) was threatened with extinction (i.e., critically endangered, endangered, or vulnerable) and 11% were near threatened. Ten percent of cetacean species were data deficient, and we predicted that 2–3 of these species may also be threatened. The proportion of threatened cetaceans has increased: 15% in 1991, 19% in 2008, and 26% in 2021. The assessed conservation status of 20% of species has worsened from 2008 to 2021, and only 3 moved into categories of lesser threat. Cetacean species with small geographic ranges were more likely to be listed as threatened than those with large ranges, and those that occur in freshwater (100% of species) and coastal (60% of species) habitats were under the greatest threat. Analysis of odontocete species distributions revealed a global hotspot of threatened small cetaceans in Southeast Asia, in an area encompassing the Coral Triangle and extending through nearshore waters of the Bay of Bengal, northern Australia, and Papua New Guinea and into the coastal waters of China. Improved management of fisheries to limit overfishing and reduce bycatch is urgently needed to avoid extinctions or further declines, especially in coastal areas of Asia, Africa, and South America.Publisher PDFPeer reviewe

The relationship between substructure in 2D X-ray surface brightness images and weak lensing mass maps of galaxy clusters: A simulation study

In this paper, we undertake a study to determine what insight can be reliably gleaned from the comparison of the X-ray and the weak lensing mass maps of galaxy clusters. We do this by investigating the 2D substructure within three high-resolution cosmological simulations of galaxy clusters. Our main results focus on non-radiative gas dynamics, but we also consider the effects of radiative cooling at high redshift. For our analysis, we use a novel approach, based on unsharp-masking, to identify substructures in 2D surface mass density and X-ray surface brightness maps. At full resolution (~ 15 h^-1 kpc), this technique is capable of identifying almost all self-bound dark matter subhaloes with M>10^12 h^-1 M_sun. We also report a correlation between the mass of a subhalo and the area of its corresponding 2D detection; such a correlation, once calibrated, could provide a useful estimator for substructure mass. Comparing our 2D mass and X-ray substructures, we find a surprising number of cases where the matching fails: around one third of galaxy-sized substructures have no X-ray counterpart. Some interesting cases are also found at larger masses, in particular the cores of merging clusters where the situation can be complex. Finally, we degrade our mass maps to what is currently achievable with weak-lensing observations (~100 h^-1 kpc at z=0.2). While the completeness mass limit increases by around an order of magnitude, a mass-area correlation remains. Our paper clearly demonstrates that the next generation of lensing surveys should start to reveal a wealth of information on cluster substructure. (Abridged)Comment: 30 pages, 27 figures, 3 tables. Accepted for publication in MNRAS. High resolution version available at http://www.physics.ox.ac.uk/users/powell/clustersubs_highres.pd

Vacteens.org: A Mobile Web app to Improve HPV Vaccine Uptake

U.S. HPV vaccine uptake remains below the Healthy People 2030 goal of 80% series completion. Parental concerns and misinformation about the efficacy and safety of the Human Papillomavirus (HPV) vaccine remain, and may be addressed by digital interventions tailored to their concerns. Reported here are results from a small scale randomized trial testing a mobile web app for parents and their adolescent daughters (ages 11-14 years) encouraging HPV vaccination in New Mexico, an ethnically-diverse U.S. state. Methods: A clinic-cluster randomized trial where pediatric clinics (n = 9) were recruited and randomized, and parent-adolescent pairs (n = 82) within clinics received either the Vacteens.org/Vacunadolescente.org mobile web app or Usual and Customary (UC) HPV Vaccination information. Parents completed online surveys at baseline and 3-months. Daughters' HPV vaccine data were collected from the New Mexico State Immunization Information System 1 year post baseline. Results: Three month survey results found Vacteens.org/Vacunadolescente.org parents to have higher positive HPV vaccine beliefs, informed decision making, intent to vaccinate and vaccine confidence outcomes than UC parents. HPV vaccine data found higher first dose HPV vaccination (Pearson χ2 = 6.13, p = 0.013, Vacteens.org/Vacunadolescente.org group 59.4%, UC group 40.6%), and higher HPV vaccination series completion (Pearson χ2 = 6.49, p = 0.011, Vacteens.org/Vacunadolescente.org group 68.4%, UC group 31.6%). Conclusions: The small trial results showed the Vacteens.org/Vacunadolescente.org web app prompted positive vaccine-related attitudes and beliefs, and more HPV vaccination initiation and series completion. Mobile web apps can make decision-making tools for HPV vaccination widely available on digital platforms, reducing vaccine hesitancy, and confusion and increase HPV vaccine uptake

KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models

BACKGROUND: In non-small cell lung cancer (NSCLC) KRAS-mutant status is a negative prognostic and predictive factor. Nitrogen-containing bisphosphonates inhibit prenylation of small G-proteins (e.g. Ras, Rac, Rho) and thus may affect proliferation and migration. In our preclinical work, we investigated the effect of an aminobisphosphonate compound (zoledronic acid) on mutant and wild type KRAS-expressing human NSCLC cell lines. RESULTS: We confirmed that zoledronic acid was unable to inhibit the prenylation of mutant K-Ras unlike in the case of wild type K-Ras. In case of in vitro proliferation, the KRAS-mutant human NSCLC cell lines showed resistance to zoledronic acid wild-type KRAS-cells proved to be sensitive. Combinatory application of zoledronic acid enhanced the cytostatic effect of cisplatin. Zoledronic acid did not induce significant apoptosis. In xenograft model, zoledronic acid significantly reduced the weight of wild type KRAS-EGFR-expressing xenograft tumor by decreasing the proliferative capacity. Futhermore, zoledronic acid induced VEGF expression and improved in vivo tumor vascularization. MATERIALS AND METHODS: Membrane association of K-Ras was examined by Western-blot. In vitro cell viability, apoptotic cell death and migration were measured in NSCLC lines with different molecular background. The in vivo effect of zoledronic acid was investigated in a SCID mouse subcutaneous xenograft model. CONCLUSIONS: The in vitro and in vivo inhibitory effect of zoledronic acid was based on the blockade of cell cycle in wild type KRAS-expressing human NSCLC cells. The zoledronic acid induced vascularization supported in vivo cytostatic effect. Our preclinical investigation suggests that patients with wild type KRAS-expressing NSCLC could potentially benefit from aminobisphosphonate therapy