The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/?-Catenin Pathway in Skin Epidermis In Vivo

The contribution of the Wnt signaling pathway to human papilloma virus (HPV)-induced carcinogenesis is poorly understood. In high-grade dysplastic lesions that are caused by high-risk HPVs (HR-HPV), ?-catenin is often located in the cell nucleus, which suggests that Wnt pathway may be involved in the development of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain of the HPV16-E6 oncoprotein induces the nuclear accumulation of ?-catenin due to its capacity to degrade PDZ-containing cellular targets. To test this hypothesis, we evaluated the staining pattern of ?-catenin in the skin epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6 mice) and measured LacZ gene expression in K14E6 mice that were crossed with a strain expressing LacZ that was knocked into the Axin2 locus (Axin2+/LacZ mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of ?-catenin, the accumulation of cellular ?-catenin–responsive genes, and the expression of LacZ. None of these effects were observed when a truncated E6 oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6?PDZ mice) or in combination with Axin2+/LacZ. Conversely, cotransfection with either E6 or E6?PDZ similarly enhanced canonical Wnt signaling in short-term in vitro assays that used a luciferase Wnt/?-catenin/TCF-dependent promoter. We propose that the activation of canonical Wnt signaling could be induced by the HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain seems to be important in in vivo models only. Mol Cancer Res; 10(2); 250–8. ©2011 AACR

Registo internacional da Iniciativa Stent-Save a Life sobre a prática de angioplastia coronária primária durante a pandemia de COVID-19

© 2021 Published by Elsevier España, S.L.U. on behalf of Sociedade Portuguesa de Cardiologia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Aim: To assess the impact of the COVID-19 pandemic on admissions of patients with acute coronary syndromes (ACS) and primary percutaneous coronary intervention (PPCI) in countries participating in the Stent-Save a Life (SSL) global initiative. Methods and results: We conducted a multicenter observational survey to collect data on patient admissions for ACS, ST-elevation myocardial infarction (STEMI) and PPCI in participating SSL member countries through a period during the COVID-19 outbreak (March and April 2020) compared with the equivalent period in 2019. Of the 32 member countries of the SSL global initiative, 17 agreed to participate in the survey (three in Africa, five in Asia, six in Europe and three in Latin America). Overall reductions of 27.5% and 20.0% were observed in admissions for ACS and STEMI, respectively. The decrease in PPCI was 26.7%. This trend was observed in all except two countries. In these two, the pandemic peaked later than in the other countries. Conclusions: This survey shows that the COVID-19 outbreak was associated with a significant reduction in hospital admissions for ACS and STEMI as well as a reduction in PPCI, which can be explained by both patient- and system-related factors.info:eu-repo/semantics/publishedVersio

The CCAT-Prime Submillimeter Observatory

The Cerro Chajnantor Atacama Telescope-prime (CCAT-prime) is a new 6-m, off-axis, low-emissivity, large field-of-view submillimeter telescope scheduled for first light in the last quarter of 2021. In summary, (a) CCAT-prime uniquely combines a large field-of-view (up to 8-deg), low emissivity telescope (< 2%) and excellent atmospheric transmission (5600-m site) to achieve unprecedented survey capability in the submillimeter. (b) Over five years, CCAT-prime first generation science will address the physics of star formation, galaxy evolution, and galaxy cluster formation; probe the re-ionization of the Universe; improve constraints on new particle species; and provide for improved removal of dust foregrounds to aid the search for primordial gravitational waves. (c) The Observatory is being built with non-federal funds (~ \$40M in private and international investments). Public funding is needed for instrumentation (~ \$8M) and operations (\$1-2M/yr). In return, the community will be able to participate in survey planning and gain access to curated data sets. (d) For second generation science, CCAT-prime will be uniquely positioned to contribute high-frequency capabilities to the next generation of CMB surveys in partnership with the CMB-S4 and/or the Simons Observatory projects or revolutionize wide-field, sub-millimetter line intensity mapping surveys.Comment: Astro2020 APC White Pape

Registo internacional da Iniciativa Stent-Save a Life sobre a prática de angioplastia coronária primária durante a pandemia de COVID-19

AIM : To assess the impact of the COVID-19 pandemic on admissions of patients with acute coronary syndromes (ACS) and primary percutaneous coronary intervention (PPCI) in countries participating in the Stent-Save a Life (SSL) global initiative. METHODS AND RESULTS : We conducted a multicenter observational survey to collect data on patient admissions for ACS, ST-elevation myocardial infarction (STEMI) and PPCI in participating SSL member countries through a period during the COVID-19 outbreak (March and April 2020) compared with the equivalent period in 2019. Of the 32 member countries of the SSL global initiative, 17 agreed to participate in the survey (three in Africa, five in Asia, six in Europe and three in Latin America). Overall reductions of 27.5% and 20.0% were observed in admissions for ACS and STEMI, respectively. The decrease in PPCI was 26.7%. This trend was observed in all except two countries. In these two, the pandemic peaked later than in the other countries. CONCLUSIONS : This survey shows that the COVID-19 outbreak was associated with a significant reduction in hospital admissions for ACS and STEMI as well as a reduction in PPCI, which can be explained by both patient- and system-related factors.OBJETIVOS : Avaliar o impacto da pandemia COVID-19 nas admissões de doentes com síndromes coronárias agudas (SCA) e angioplastia coronária primária (PPCI) em países que participam da iniciativa global Stent-Save a Life (SSL). METODOS e RESULTADOS : Realizámos estudo observacional multicêntrico para coletar dados sobre admissões de doentes por ACS, STEMI e PPCI nos países participantes no SSL durante um período do surto COVID-19 (março e abril de 2020) em comparação com o período homólogo de 2019. Dos 32 países membros da iniciativa global SSL, 17 aceitaram participar no estudo (3 de África, 5 da Ásia, 6 da Europa e 3 da América Latina (LATAM)). Observámos uma redução global de 27,5% e 20,0% nos internamentos com SCA e STEMI, respetivamente. A diminuição do PPCI foi de 26,7%. Essa tendência foi observada em todos os países, exceto dois. Nestes dois países, a pandemia atingiu o pico mais tarde do que nos restantes. CONCLUSOES : Este estudo mostra que o surto de COVID-19 foi associado a uma redução significativa de admissões hospitalares por SCA e STEMI, bem como uma redução de PPCI, o que pode ser explicado por fatores relacionados com o doente e com o sistema.https://www.journals.elsevier.com/revista-portuguesa-de-cardiologia/dm2022Family Medicin

SCOPE : SCUBA-2 Continuum Observations of Pre-protostellar Evolution - survey description and compact source catalogue

We present the first release of the data and compact-source catalogue for the JCMT Large Program SCUBA-2 Continuum Observations of Pre-protostellar Evolution (SCOPE). SCOPE consists of 850 mu m continuum observations of 1235 Planck Galactic Cold Clumps (PGCCs) made with the Submillimetre Common-User Bolometer Array 2 on the James Clerk Maxwell Telescope. These data are at an angular resolution of 14.4 arcsec, significantly improving upon the 353 GHz resolution of Planck at 5 arcmin, and allowing for a catalogue of 3528 compact sources in 558 PGCCs. We find that the detected PGCCs have significant sub-structure, with 61 per cent of detected PGCCs having three or more compact sources, with filamentary structure also prevalent within the sample. A detection rate of 45 per cent is found across the survey, which is 95 per cent complete to Planck column densities of N-H2 > 5 x10(21) cm(-2). By positionally associating the SCOPE compact sources with young stellar objects, the star formation efficiency, as measured by the ratio of luminosity to mass, in nearby clouds is found to be similar to that in the more distant Galactic Plane, with the column density distributions also indistinguishable from each other.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks