Control of 3' splice site selection by the yeast splicing factor Fyv6.

Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1 and 2 step factors). We recently identified Fyv6 (FAM192A in humans) as a 2 step factor in ; however, we did not determine how widespread Fyv6's impact is on the transcriptome.

Functional analysis of the zinc finger modules of the splicing factor Luc7.

Identification of splice sites is a critical step in pre-messenger RNA (pre-mRNA) splicing because the definition of the exon/intron boundaries controls what nucleotides are incorporated into mature mRNAs. The intron boundary with the upstream exon is initially identified through interactions with the U1 small nuclear ribonucleoprotein (snRNP). This involves both base-pairing between the U1 snRNA and the pre-mRNA as well as snRNP proteins interacting with the 5' splice site (5'ss)/snRNA duplex.

Functional Analysis of the Zinc Finger Modules of the Splicing Factor Luc7.

Identification of splice sites is a critical step in pre-mRNA splicing since definition of the exon/intron boundaries controls what nucleotides are incorporated into mature mRNAs. The intron boundary with the upstream exon is initially identified through interactions with the U1 snRNP. This involves both base pairing between the U1 snRNA and the pre-mRNA as well as snRNP proteins interacting with the 5' splice site/snRNA duplex.

Facilitating increased participation in clinical trials: what do consumers expect of clinical trial matching websites?

Clinical trials offer access to novel therapies and potential major benefits for patients, but identifying and accessing suitable trials remains a significant challenge for consumers. A burgeoning range of online services aims to meet this need; however, there is a paucity of data on whether these services are addressing the requirements and concerns of consumers. Here, we report our findings from a survey of cancer consumers, with results we believe are relevant to the broader research community.

Does the registry speak your language? A case study of the Global Angelman Syndrome Registry.

Global disease registries are critical to capturing common patient related information on rare illnesses, allowing patients and their families to provide information about their condition in a safe, accessible, and engaging manner that enables researchers to undertake critical research aimed at improving outcomes. Typically, English is the default language of choice for these global digital health platforms. Unfortunately, language barriers can significantly inhibit participation from non-English speaking participants.

Hospital length of stay prediction tools for all hospital admissions and general medicine populations: systematic review and meta-analysis.

Background: Unwarranted extended length of stay (LOS) increases the risk of hospital-acquired complications, morbidity, and all-cause mortality and needs to be recognized and addressed proactively.

Objective: This systematic review aimed to identify validated prediction variables and methods used in tools that predict the risk of prolonged LOS in all hospital admissions and specifically General Medicine (GenMed) admissions.

Method: LOS prediction tools published since 2010 were identified in five major research databases.

Biochemical and genetic evidence supports Fyv6 as a second-step splicing factor in .

Precursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of five small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density.

Hospital length of stay prediction for general surgery and total knee arthroplasty admissions: Systematic review and meta-analysis of published prediction models.

Objective: Systematic review of length of stay (LOS) prediction models to assess the study methods (including prediction variables), study quality, and performance of predictive models (using area under receiver operating curve (AUROC)) for general surgery populations and total knee arthroplasty (TKA).

Method: LOS prediction models published since 2010 were identified in five major research databases. The main outcomes were model performance metrics including AUROC, prediction variables, and level of validation.

Biochemical and Genetic Evidence Supports Fyv6 as a Second-Step Splicing Factor in .

Precursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of 5 small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density.

Moving with the Times: The Health Science Alliance (HSA) Biobank, Pathway to Sustainability.

Human biobanks are recognised as vital components of translational research infrastructure. With the growth in personalised and precision medicine, and the associated expansion of biomarkers and novel therapeutics under development, it is critical that researchers can access a strong collection of patient biospecimens, annotated with clinical data. Biobanks globally are undertaking transformation of their operating models in response to changing research needs; transition from a 'classic' model representing a largely retrospective collection of pre-defined specimens to a more targeted, prospective collection model, although there remains a research need for both models to co-exist.

Normalising comparative effectiveness trials as clinical practice.

There is a lack of high-quality evidence underpinning many contemporary clinical practice guidelines embedded in the healthcare systems, leading to treatment uncertainty and practice variation in most medical disciplines. Comparative effectiveness trials (CETs) represent a diverse range of research that focuses on optimising health outcomes by comparing currently approved interventions to generate high-quality evidence to inform decision makers. Yet, despite their ability to produce real-world evidence that addresses the key priorities of patients and health systems, many implementation challenges exist within the healthcare environment.

Ethics and regulatory considerations for the clinical translation of somatic cell human epigenetic editing.

Altering the human epigenome with gene-editing technology in attempt to treat a variety of diseases and conditions seems scientifically feasible. We explore some of the ethical and regulatory issues related to the clinical translation of human epigenetic editing arguing that such approaches should be considered akin to somatic therapies.

Review of research output of Australian and New Zealand colorectal surgeons over the past 20 years.

Objectives: High-quality research has a tangible impact on patient care and should inform all medical decision-makings. Appraising and benchmarking of research is necessary in evidence-based medicine and allocation of funding. The aim of this review is to demonstrate how evidence may be gathered by quantifying the amount and type of research by a group of surgeons over a 20-year period.

A platform in the use of medicines to treat chronic hepatitis C (PLATINUM C): protocol for a prospective treatment registry of real-world outcomes for hepatitis C.

Background: Safe, highly curative, short course, direct acting antiviral (DAA) therapies are now available to treat chronic hepatitis C. DAA therapy is freely available to all adults chronically infected with the hepatitis C virus (HCV) in Australia. If left untreated, hepatitis C may lead to progressive hepatic fibrosis, cirrhosis and hepatocellular carcinoma.

International Policy Frameworks for Consent in Minimal-risk Pragmatic Trials.

There is intense debate around the use of altered and waived consent for pragmatic trials. Those in favor argue that traditional consent compromises the internal and external validity of these trials. Those against, warn that the resultant loss of autonomy compromises respect for persons and could undermine trust in the research enterprise.

Exploring pathways towards improving patient experience of robot-assisted radical prostatectomy (RARP): assessing patient satisfaction and attitudes.

Objective: To determine patient satisfaction and experience after robot-assisted radical prostatectomy (RARP) for prostate cancer, using a convergent mixed-method qualitative analysis approach.

Patients And Methods: 412 patients who underwent RARP between January 2014 and June 2016 were mailed questionnaires and invited to participate in focus groups. Qualitative data was thematically analysed using NVivo.

Corrigendum: Whole-genome landscape of pancreatic neuroendocrine tumours.

This corrects the article DOI: 10.1038/nature21063.

Lost in translation: returning germline genetic results in genome-scale cancer research.

Background: The return of research results (RoR) remains a complex and well-debated issue. Despite the debate, actual data related to the experience of giving individual results back, and the impact these results may have on clinical care and health outcomes, is sorely lacking. Through the work of the Australian Pancreatic Cancer Genome Initiative (APGI) we: (1) delineate the pathway back to the patient where actionable research data were identified; and (2) report the clinical utilisation of individual results returned.

CHIP/Stub1 regulates the Warburg effect by promoting degradation of PKM2 in ovarian carcinoma.

Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis.

Design of a framework for the deployment of collaborative independent rare disease-centric registries: Gaucher disease registry model.

Orphan drug clinical trials often are adversely affected by a lack of high quality treatment efficacy data that can be reliably compared across large patient cohorts derived from multiple governmental and country jurisdictions. It is critical that these patient data be captured with limited corporate involvement. For some time, there have been calls to develop collaborative, non-proprietary, patient-centric registries for post-market surveillance of aspects related to orphan drug efficacy.

Prevention of postsurgical wound dehiscence after abdominal surgery with NPWT: a multicentre randomised controlled trial protocol.

Objective: The effectiveness of negative pressure wound therapy (NPWT) in the prevention of postoperative surgical wound dehiscence (SWD) is the subject of much debate and remains to be determined. This study will identify individuals at risk of postoperative SWD and trial the use of NPWT as a prophylactic measure against the occurrence of SWD, compared with a non-NPWT standard surgical dressing (SSD).

Method: A prospective multicentre randomised controlled trial comparing NPWT dressing against standard surgical dressings (SSD) will be conducted.