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These results suggest that the v-Src modifies cytotoxicities of anticancer drugs targeting cell division. Highly activated Src-induced resistance to MTAs through mitotic slippage might have a risk to enhance the malignancy of cancer cells through the increase in chromosome instability upon chemotherapy using MTAs.

The aim of this review was to evaluate the reporting and methodological quality of systematic reviews and meta-analyses (SRs/MAs) on nursing interventions in patients with chronic obstructive pulmonary disease (COPD) and to determine potential factors that predict high quality.

The review is a quantitative systematic review.

PubMed, Embase and the Cochrane Database of Systematic Reviews.

A comprehensive literature search was conducted in three databases for SRs/MAs published up to 6 May 2020. The PRISMA statement and AMSTAR checklist were used to evaluate the reporting and methodological quality.

A total of 130 articles published between 1996-2020 from 69 journals were included in this review. Multivariate regression analyses demonstrated that the following factors were related to the higher reporting quality of included articles having a protocol or registration and being published on the Cochrane Database of Systematic Reviews. Systematic reviews including meta-analyses, number of authors >5, n medical and health practice.

The SMART (Strategic MAnagement to optimize response to cardiac Resynchronization Therapy) Registry was designed to assess real-world outcomes for patients receiving a cardiac resynchronization therapy defibrillator (CRT-D) and to better understand which programming and optimization techniques are used and how effective they are.

The SMART Registry is a global, multicentre, prospective, observational, post-market CRT-D registry with a planned enrolment of 2000 subjects from a maximum of 200 sites in Europe, North America, and Asia-Pacific region. Each subject will be followed up for a minimum of 12months. The primary endpoint of CRT response rate at 12months is defined by a clinical composite score of all-cause mortality, heart failure events, New York Heart Association Class, and quality of life as assessed by a patient global assessment instrument. A subgroup composed of the first 103 consecutive European subjects implanted with an NG4 device will have left ventricular multisite pacing feature enabled at any time during the initial 12months of follow-up. The primary endpoint for this sub-analysis will be the NG4 PG-related complication-free rate at 36months.

The SMART Registry achieved its recruitment target in August 2019, with 2014 patients enrolled. see more The baseline demographics demonstrated that patients were generally older, with greater co-morbidity, and on more contemporary medical therapy than in the key CRT trials. The results of the SMART Registry will determine which programming and optimization techniques are effective in this real-world population.

The SMART Registry achieved its recruitment target in August 2019, with 2014 patients enrolled. The baseline demographics demonstrated that patients were generally older, with greater co-morbidity, and on more contemporary medical therapy than in the key CRT trials. The results of the SMART Registry will determine which programming and optimization techniques are effective in this real-world population.

RAS short variant (SV) mutations in colorectal cancer (CRC) are associated with lack of benefit from epidermal growth factor receptor (EGFR) monoclonal antibody (EGFRmAb). However, the clinical implications for RAS amplification (RASa) as a biomarker for anti-EGFR therapy in CRC remain ill defined.

Genomic analysis was performed using the Foundation Medicine (FM) comprehensive genomic profiling database of 37,233 CRC cases. Clinical outcomes were assessed using two independent cohorts the City of Hope (COH) cohort of 338 patients with metastatic CRC (mCRC) and the Flatiron Health-FM real-world clinicogenomic database (CGDB) of 3,904 patients with mCRC.

RASa was detected in 1.6% (614/37,233) of primarily mCRC. RASa 6-9 (n = 241, 39%), 10-19 (n = 165, 27%), and ≥ 20 (n = 209, 34%) copy number subsets had co-RAS SV/BRAF V600E in 63%/3%, 31%/0.6%, and 4.8%/0% of cases, respectively. In the COH cohort, six patients with RASa (13-54 copies) received EGFRmAb, four of six had progressive disease, two had stable may function similarly to RAS mutation as a negative predictor of benefit from anti-epidermal growth factor receptor therapies in colorectal cancer. More clinical data are needed, and comprehensive genomic profiling, including detection of RAS amplification, should be used in trial design to inform therapy selection.

1% of colorectal cancer cases and that degree of amplification inversely correlates with co-occurring MAPK pathway alterations. Preliminary clinical evidence suggests that RAS amplification may function similarly to RAS mutation as a negative predictor of benefit from anti-epidermal growth factor receptor therapies in colorectal cancer. More clinical data are needed, and comprehensive genomic profiling, including detection of RAS amplification, should be used in trial design to inform therapy selection.ELX-02 is an investigational compound being developed as a therapy for genetic diseases caused by nonsense mutations such as cystic fibrosis. Structurally, ELX-02 is an aminoglycoside analogue that induces read-through of nonsense mutations through interaction with the ribosome, resulting in the production of full-length functional proteins. This phase 1 multiple-ascending-dose trial evaluated the safety and pharmacokinetics of ELX-02 in 62 healthy volunteers. ELX-02 plasma exposure was dose proportional, with no apparent accumulation, and followed by renal elimination. The most reported adverse event was injection site reactions that were mild to moderate in severity. At the top dose of 5.0 mg/kg, 1 of 6 subjects experienced auditory threshold changes in which ototoxicity could not be clearly ruled out, and 2 of 6 had hearing threshold changes consistent with possible ototoxicity. Two of 3 subjects receiving placebo in the 5.0 mg/kg group also had significant hearing threshold changes. All observed hearing threshold changes resolved or were trending toward resolution after withdrawal of the study drug.

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