The Kety-Schmidt Technique for Quantitative Perfusion and Oxygen Metabolism Measurements in the MR Imaging Environment

The Kety-Schmidt technique provides quantitative measurement of whole brain cerebral blood flow (CBF). CBF is measured as the area between the arterial and venous washout curves of a diffusible tracer. Oxygen extraction and metabolism may be calculated from arterial and venous samples. In this report we present a method for performing these measurements in an MR environment. This technique could be useful for validation of MR methods of hemodynamic and metabolic measurements in humans

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Which outcomes are most important to measure in patients with COVID-19 and how and when should these be measured? Development of an international standard set of outcomes measures for clinical use in patients with COVID-19: a report of the International Consortium for Health Outcomes Measurement (ICHOM) COVID-19 Working Group

Objectives: The COVID-19 pandemic has resulted in widespread morbidity and mortality with the consequences expected to be felt for many years. Significant variation exists in the care even of similar patients with COVID-19, including treatment practices within and between institutions. Outcome measures vary among clinical trials on the same therapies. Understanding which therapies are of most value is not possible unless consensus can be reached on which outcomes are most important to measure. Furthermore, consensus on the most important outcomes may enable patients to monitor and track their care, and may help providers to improve the care they offer through quality improvement. To develop a standardised minimum set of outcomes for clinical care, the International Consortium for Health Outcomes Measurement (ICHOM) assembled a working group (WG) of 28 volunteers, including health professionals, patients and patient representatives. Design: A list of outcomes important to patients and professionals was generated from a systematic review of the published literature using the MEDLINE database, from review of outcomes being measured in ongoing clinical trials, from a survey distributed to patients and patient networks, and from previously published ICHOM standard sets in other disease areas. Using an online-modified Delphi process, the WG selected outcomes of greatest importance. Results: The outcomes considered by the WG to be most important were selected and categorised into five domains: (1) functional status and quality of life, (2) mental functioning, (3) social functioning, (4) clinical outcomes and (5) symptoms. The WG identified demographic and clinical variables for use as case-mix risk adjusters. These included baseline demographics, clinical factors and treatment-related factors. Conclusion: Implementation of these consensus recommendations could help institutions to monitor, compare and improve the quality and delivery of care to patients with COVID-19. Their consistent definition and collection could also broaden the implementation of more patient-centric clinical outcomes research

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Cianoacrilato na colagem de Bráquetes ortodônticos em resina acrílica: há maior adesão?

Pacientes em tratamento ortodôntico apresentam restaurações provisórias com frequência. No entanto, poucos estudos avaliam a influência dos adesivos na resistência ao cisalhamento dos bráquetes nessas superfícies. A resina acrílica é comumente indicada para colagem de bráquetes, porém o uso do cianoacrilato como adesivo ortodôntico é uma opção analisada. O objetivo do presente trabalho foi avaliar o desempenho do cianoacrilato associado aos materiais comumente utilizados para a fixação de bráquetes metálicos em restaurações provisórias de resina acrílica. Quarenta amostras em resina acrílica foram preparadas e as superfícies homogeinizadas com lixas de carboneto de silício (320 e 600). Em seguida, as amostras foram divididas aleatoriamente em quatro grupos (n=10) com base no tratamento de superfície e agente de união: G1 - bráquetes colados com resina acrílica; G2 - bráquetes colados com resina acrílica e aplicação de cianoacrilato; G3 - bráquetes colados com Transbond(tm) XT; G4 - bráquetes colados com Transbond(tm) XT e aplicação de cianoacrilato. Foram utilizados bráquetes ortodônticos de aço inoxidável, prescrição Roth, Kirium (3M/Abzil) para incisivos centrais superiores direitos, slot 022. Após colagem, as amostras foram submetidas ao teste de cisalhamento a uma velocidade de 0,5mm/min em uma máquina de ensaios universal (EMIC DL-1000). Os dados foram coletados e submetidos à análise estatística pelo teste ANOVA com nível de significância de 5%. A associação de resina acrílica ao cianoacrilato (G2) resultou na maior resistência ao cisalhamento (13,76 MPa), mas não significativa em comparação aos valores obtidos para a resina acrílica (G1= 7,76 MPa). O mesmo pôde ser observado para a associação Transbond(tm) XT e cianoacrilato (G4= 4,03 MPa) em relação a utilização da Transbond(tm) XT de forma isolada (G3= 3,87 MPa) e resina acrílica. O tratamento de superfície tem efeito significativo na resistência da união dos bráquetes colados aos materiais provisórios. A associação de cianoacrilato ao monômero de metilmetacrilato apresentou maior resistência ao cisalhamento, sendo mais indicada clinicamente

Metarrestin, a perinucleolar compartment inhibitor, effectively suppresses metastasis

Metastasis remains a leading cause of cancer mortality due to the lack of specific inhibitors against this complex process. To identify compounds selectively targeting the metastatic state, we used the perinuclear compartment (PNC), a complex nuclear structure associated with metastatic behaviors of cancer cells, as a phenotypic marker for a high-content screen of over 140,000 structurally diverse compounds. Metarrestin, obtained through optimization of a screening hit, disassembles PNCs in multiple cancer cell lines, inhibits invasion in vitro, suppresses metastatic development in three mouse models of human cancer, and extends survival of mice in a metastatic pancreatic cancer xenograft model with no organ toxicity or discernable adverse effects. Metarrestin disrupts the nucleolar structure and inhibits RNA polymerase (Pol) I transcription, at least in part by interacting with the translation elongation factor eEF1A2. Thus, metarrestin represents a potential therapeutic approach for the treatment of metastatic cancer