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The use of observational analyses, such as classical epidemiological studies or randomised controlled trials (RCTs), to infer causality in cancer may be problematic due to both ethical reasons and technical issues, such as confounding variables and reverse causation. Mendelian randomisation (MR) is an epidemiological technique that uses genetic variants as proxies for exposures in an attempt to determine whether there is a causal link between an exposure and an outcome. Given that genetic variants are randomly assigned during meiosis according to Mendel’s first and second laws of heritability, MR may be thought of as a ‘natural’ RCT and is therefore less vulnerable to the aforementioned problems. MR has the potential to help identify new, and validate or disprove previously implicated, modifiable risk factors in cancer, but it is not without limitations. This review gives a brief description of the history and principles of MR, as well as a guide to basic MR methodology. The bulk of the review then examines various limitations of MR in more detail, discussing some of the proposed solutions to these problems. The review ends with a brief section detailing the practical implementation of MR, with examples of its use in the study of cancer, and an assessment of its utility in identifying cancer predisposition traits. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The oncogene brachyury (TBXT) is a T-box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not previously been investigated in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples. Our glioma samples were analyzed for copy number (n = 372), promoter methylation status (n = 170), and mutation status (n = 1569 tissues and n = 52 cell lines) of the brachyury gene. The prognostic impact of brachyury expression was studied in 1524 glioma patient tumors. The functional impact of brachyury on glioma proliferation, viability, and cell death was evaluated both in vitro and in vivo. Brachyury was expressed in the normal brain, and significantly downregulated in gliomas tissues. Loss of brachyury was associated with tumor aggressiveness and poor survival in glioma patients. Downregulation of brachyury was not associated with gene deletion, promoter methylation, or inactivating point mutations. Brachyury re-expression in glioma cells was found to decrease glioma tumorigenesis by induction of autophagy. These data strongly suggest that brachyury behaves as a tumor suppressor gene in gliomas by modulating autophagy. Importantly, brachyury constitutes an independent positive biomarker of patient prognosis. Our findings indicate that the role of brachyury in tumorigenesis may be tissue-dependent and demands additional investigation to guide rational interventions. This article is protected by copyright. All rights reserved. RGDpeptide This article is protected by copyright. All rights reserved.BACKGROUND Prehospital hemorrhagic shock accounts for approximately 25,000 civilian deaths annually in the United States. A balanced, blood-based resuscitation strategy is hypothesized to be the optimal treatment for these patients. Due to logistical constraints, delivering a balanced, blood-based resuscitation is difficult in the prehospital setting. A low titer O+ whole blood (LTO+ WB) ground ambulance initiative, may help alleviate this capability gap. CASE REPORT A 37-year-old female was involved in a motor vehicle collision at approximately 1630. While she was trapped inside the vehicle, her mental status deteriorated. The patient was successfully extricated at 1704 and found to be in cardiac arrest. The paramedics and firefighters quickly secured her airway and applied a mechanical CPR device. The first responder team obtained return of spontaneous circulation, but the patient’s blood pressure was 43/27 mmHg. The paramedics transfused one unit of LTO+ WB. Twenty-one minutes after the initial LTO+ WB transfusion, the air ambulance team transfused a second unit of LTO+ WB. Upon hospital arrival, the transfusion was completed, and the patient’s shock index improved to 1.0. The trauma team identified a grade 5 splenic injury with active extravasation. Interventional radiology performed an angiogram and successfully embolized the tertiary branches of the inferior splenic pole. She was extubated on postinjury Day one and discharged to her home neurologically intact on postinjury Day 12. CONCLUSION The prehospital availability of LTO+ WB may enhance the resuscitation of critically ill trauma patients. © 2020 AABB.BACKGROUND Pleiotrophin (PTN) and midkine (MK) are cytokines that are up-regulated in the prefrontal cortex (PFC) after alcohol administration and have been shown to reduce alcohol intake and reward. Both cytokines are endogenous inhibitors of receptor protein tyrosine phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1). Recently, a new compound named MY10 was designed with the aim of mimicking the activity of PTN and MK. MY10 has already shown promising results regulating alcohol-related behaviors in mice. METHODS We have now tested the effects of MY10 on alcohol operant self-administration and Drinking In the Dark-Multiple Scheduled Access (DID-MSA) paradigms in rats. Gene expression of relevant genes in the PTN/MK signaling pathway in the PFC was analyzed by real-time PCR. RESULTS MY10, at the highest dose tested (100 mg/kg), reduced alcohol consumption in the alcohol operant self-administration paradigm (p = 0.040). In the DID-MSA paradigm, rats drank significantly less alcohol (p = 0.019) and showed a significant decrease in alcohol preference (p = 0.002). We observed that the longer the exposure to alcohol, the greater the suppressing effects of MY10 on alcohol consumption. It was demonstrated that the effects of MY10 were specific to alcohol since saccharin intake was not affected by MY10 (p = 0.804). MY10 prevented the alcohol-induced down-regulation of Ptprz1 (p = 0.004) and anaplastic lymphoma kinase (Alk; p = 0.013) expression. CONCLUSIONS Our results support and provide further evidence regarding the efficacy of MY10 on alcohol-related behaviors and suggest the consideration of the blockade of RPTPβ/ζ as a target for reducing excessive alcohol consumption. © 2020 by the Research Society on Alcoholism.