Glioblastoma multiforme (GBM) is the most common primary brain cancer. GBMs commonly acquire resistance to standard-of-care therapies. Among the novel means to sensitize GBM to DNA-damaging therapies, a promising strategy is to combine them with inhibitors of the DNA damage repair (DDR) machinery, such as inhibitors for poly(ADP-ribose) polymerase (PARP). PARP inhibitors (PARPis) have already shown efficacy and have received regulatory approval for breast, ovarian, prostate, and pancreatic cancer treatment. In these cancer types, after PARPi administration, patients carrying specific mutations in the breast cancer 1 (BRCA1) and 2 (BRCA2) suppressor genes have shown better response when compared to wild-type carriers. Mutated BRCA genes are infrequent in GBM tumors, but their cells can carry other genetic alterations that lead to the same phenotype collectively referred to as ‘BRCAness’. The most promising biomarkers of BRCAness in GBM are related to isocitrate dehydrogenases 1 and 2 (IDH1/2), epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN), MYC proto-oncogene, and estrogen receptors beta (ERβ). BRCAness status identified by accurate biomarkers can ultimately predict responsiveness to PARPi therapy, thereby allowing patient selection for personalized treatment. This review discusses potential biomarkers of BRCAness for a ‘precision medicine’ of GBM patients.
Su m á r i o : 1. Introdução; 2. A importância de informações sobre custos para a melhoria da qualidade do gasto público; 3. Motivações e objetivos para a adoção de regimes contábeis que gerem informações sobre os custos do governo; 4. A adoção da contabilidade de competência deve levar necessariamente à adoção também de um orçamento de competência?; 5. O debate atual: da informação à decisão; 6. A experiência internacional e as diretrizes para adoção de um sistema de custos no setor público brasileiro; 7. Síntese e conclusões.Su m m a ry : 1. Introduction; 2. The importance of cost information for the improvement of public expenditure; 3. Motives and goals of accounting regimes that manage government expenditure information; 4. The adoption of accrual accounting must necessarily also lead to accrual budgeting?; 5. The current debate: from information to decision; 6. International experience and the guidelines for the adoption of a costing system in the Brazilian public sector; 7. Summary and conclusions.
As of the 1988 Constitution, the states, by means of a constitutional amendment, may establish metropolitan regions in order to integrate the organization, planning and operation of public functions of common interest of the states and their respective municipalities. Despite some attempts to overcome financial troubles through better coordination of public actions - new proposals for dealing with a more constrained financial situation -, difficulties of institutional character and the fragmentation of the available resources did not allow for significant improvements to be made to date. This paper intends to provide a background to understanding the problems of metropolitan financing in Brazil, which is necessary to deal with the obstacles still existing to the improvement of investments financing and service provision.
The Brazilian economy: recent developments and future prospectsThe s were years of disruption for the Brazilian economy. Attempts to overcome the negative impacts of the second oil shock in the early years of the decade, by provoking a deep recession, were quickly followed by an inflationary upsurge that was met by traumatic heterodox anti-inflationary measures. The roller-coaster path traced by GDP over the decade led nowhere. When it was over, Brazilians were no better off. Per capita income remained at the level reached in .From an economic point of view, the s were a lost decade. Unstable domestic conditions and opportunities to obtain better returns from speculative financial operations turned investors away from productive applications of capital. The investment ratio dropped to its lowest since the beginning of the s, hitting bottom in at a meagre per cent of GDP. And yet, in a well-protected domestic market, the technological gap created by the lack of an adequate level of investment was not perceived as an immediate problem by Brazilian entrepreneurs. In a highly inflationary context, in which consumers had lost any idea of the real value of money, the cost of inefficiency was easily passed on through higher prices.The country's defaulting on its external debt helped to make things worse. Access to foreign capital was blocked from the mid-s and was restored only after a long and difficult period of negotiation that did not end until . Investment from abroad almost disappeared in the late s, recovering to a figure near the $ billion mark only in the last year of the decade.The disruptive effects of the unsuccessful attempts to curb inflation almost led to the collapse of the state. Eroded by inflation, tax revenues shrank, bringing the overall tax ratio in the s down to per cent of GDP, almost ten percentage points below the peak of the mid-s.The widening gap between expenditures and revenues was filled by the hidden tax of inflation and an increase in the public debt, which, in turn, drained resources from the public services as ever greater sums were required to service the higher government debt. The final blow to the public sector came in the early s, when a disastrous administrative reform, coupled with a demoralizing wage policy for International Affairs , () - FERNANDO REZENDE Fernando Rezende The 'Real Plan' acquired its name from the new currency adopted in Brazil as a result of monetary reform implemented in July .This reform was the cornerstone of the policies adopted to bring monetary stabilization to the Brazilian economy. Since its implementation, the 'Plan' achieved its main goal of bringing the inflation rate down to more manageable levels, but other aspects of macroeconomic stability, such as fiscal and external accounts, are still waiting for the conclusion of structural reforms.
A redefinição do papel do Estado e a demarcação das responsabilidades do setor público constituem a base sobre a qual deve assentar-se a proposta da reformulação de seu padrão de financiamento. Nesse sentido, o trabalho defende um modelo de Reforma Tributária determinado pela redução do número de tributos, pela redefinição de suas bases de incidência, pelo respeito ao direito do contribuinte, pela estabilidade normativa e pela recuperação da ética tributária.
In this case study, the authors describe peculiar bilateral cotton wool-like retinal lesions associated with macular edema in a patient with COVID-19 who was vaccinated with a single dose of AstraZeneca one month earlier. This patient had no pulmonary or systemic cardiovascular complications from COVID-19, as reported in other papers that found retinal lesions. However, the patient was diagnosed with idiopathic myopathy when discovering the SARS-CoV-2 infection. The patient was a 22-year-old white female with no previous history of morbidity, complaining of blurred vision in both eyes seven days after testing positive for SARS-CoV-2 by PCR (using nasal and oral swab) and confirmed through ELISA blood test (IgM positive). There was no ancillary test revealing diabetes mellitus. The patient presented with scattered whitish cotton wool-like lesions and a few hemorrhages on the posterior pole in fundus examination. On spectral domain optical coherence tomography (SD-OCT), there were hyperreflective lesions in the nerve fiber layer, ganglion cell layer, inner nuclear layer, and inner and outer plexiform layers at the site corresponding to the whitish cotton wool-like lesions in the posterior fundus photos. Moreover, the macula of both eyes had intraretinal and subretinal fluid, reversible with corticosteroid therapy. In conclusion, COVID-19 has been associated with capillary disorders at different target sites such as retina, lungs, and central nervous system. Similarly, vaccination against SARS-CoV-2 has been linked to retinal complications in the literature; however, cotton wool-like lesions have not yet been reported. There are many questions yet to be answered about the implications of COVID-19 infection and its vaccines.
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