Controversies around the function of LARP1.

The RNA-binding protein LARP1 has generated interest in recent years for its role in the mTOR signalling cascade and its regulation of terminal oligopyrimidine (TOP) mRNA translation. Paradoxically, some scientists have shown that LARP1 represses TOP translation while others that LARP1 activates it. Here, we present opinions from four leading scientists in the field to discuss these and other contradictory findings.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

Background: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017.

Methods: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations.

Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer.

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non-small cell lung cancer (mNSCLC) has not been explored.

Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.

Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial.

Importance: Consolidative programmed death ligand-1 (PD-L) inhibition after chemoradiotherapy improves overall survival and progression-free survival (PFS) for stage III non-small cell lung cancer (NSCLC) and requires safety evaluation for incorporation of programmed cell death 1 (PD-1) inhibition at the onset of chemoradiotherapy.

Objective: To determine the safety and tolerability of PD-1 inhibition concurrently with definitive chemoradiotherapy for NSCLC.

Design, Setting, And Participants: This phase 1 prospective multicenter nonrandomized controlled trial using a 3 plus 3 design was performed from August 30, 2016, to October 24, 2018, with a median follow-up of 16.

Viscoelastic and chemical properties of dentine after different exposure times to sodium hypochlorite, ethylenediaminetetraacetic acid and calcium hydroxide.

This study aims to evaluate the viscoelastic and chemical properties of dentine after different durations of exposure to 5.25% NaOCl, 17% EDTA and Ca(OH) solutions, and NaOCl in alternating combination with EDTA. Standard dentine bars were randomly assigned to: (i) formal-saline control-1; (ii) NaOCl; (iii) EDTA; (iv) NaOCl/EDTA; (v) formal-saline control-2; (vi) Ca(OH) pH 12.

Comparison of Eight Technologies to Determine Genotype at the UGT1A1 (TA) Repeat Polymorphism: Potential Clinical Consequences of Genotyping Errors?

To ensure accuracy of (rs3064744) genotyping for use in pharmacogenomics-based irinotecan dosing, we tested the concordance of several commonly used genotyping technologies. Heuristic genotype groupings and principal component analysis demonstrated concordance for Illumina sequencing, fragment analysis, and fluorescent PCR. However, Illumina sequencing and fragment analysis returned a range of fragment sizes, likely arising due to PCR "slippage".

6'-Methoxy Raloxifene-analog enhances mouse bone properties with reduced estrogen receptor binding.

Raloxifene (RAL) is an FDA-approved drug used to treat osteoporosis in postmenopausal women. RAL suppresses bone loss primarily through its role as a selective estrogen receptor modulator (SERM). This hormonal estrogen therapy promotes unintended side effects, such as hot flashes and increased thrombosis risk, and prevents the drug from being used in some patient populations at-risk for fracture, including children with bone disorders.

Twenty-five-Year Follow-up of a Prospective Randomized Trial Comparing Preoperative Versus Postoperative FLAC/Granulocyte Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer.

Background: Preoperative chemotherapy is important in the management of women with breast cancer, with the ability to downstage the breast primary tumor and axillary lymph nodes. Long-term studies are needed to identify late toxicities, recurrence patterns, and equivalency with postoperative chemotherapy for recurrence-free survival (RFS) and overall survival (OS).

Patients And Methods: We conducted a single-institution prospective randomized control trial comparing preoperative or postoperative fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor chemotherapy for women with untreated clinical stage II (T1N1, T2N0, and T2N1) breast cancer.

Dose to Highly Functional Ventilation Zones Improves Prediction of Radiation Pneumonitis for Proton and Photon Lung Cancer Radiation Therapy.

Purpose: We hypothesized that the radiation dose in high-ventilation portions of the lung better predicts radiation pneumonitis (RP) outcome for patients treated with proton radiation therapy (PR) and photon radiation therapy (PH).

Methods And Materials: Seventy-four patients (38 protons, 36 photons) with locally advanced non-small cell lung cancer treated with concurrent chemoradiation therapy were identified, of whom 24 exhibited RP (graded using Common Terminology Criteria for Adverse Events v4.0) after PR or PH, and 50 were negative controls.

Circulating Tumor Cells Are Associated with Recurrent Disease in Patients with Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy.

Purpose: Although stereotactic body radiotherapy (SBRT) is effective in early-stage non-small cell lung cancer (NSCLC), approximately 10%-15% of patients will fail regionally and 20%-25% distantly. We evaluate a novel circulating tumor cell (CTC) assay as a prognostic marker for increased risk of recurrence following SBRT.

Experimental Design: Ninety-two subjects (median age, 71 years) with T1a (64%), T1b (23%), or T2a (13%) stage I NSCLC treated with SBRT were prospectively enrolled.

Interpreters in Health Care: A Concise Review for Clinicians.

Health care providers are frequently faced with the challenge of caring for patients who have limited English proficiency. These patients experience challenges accessing health care and are at higher risk of receiving suboptimal health care than native English speakers. Health care interpreters are crucial partners to help break down communication barriers and prevent these patients from facing health care disparities.

Type 1 diabetes: genes associated with disease development.

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030.

Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience.

Background: Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is routinely guided by fluoroscopy and utilizes contrast injection to ensure catheter positioning and pulmonary vein occlusion. Non-fluoroscopic imaging techniques including electromagnetic mapping (EM) and intracardiac echocardiography (ICE) have demonstrated reduced fluoroscopy times and contrast exposure. Utilization of color flow Doppler to evaluate vein occlusion with the balloon has not been evaluated as an alternative to contrast injection.

Measuring Psychological Change and Predicting Recidivism Following the Swedish One-to-One Program.

The One-to-One program aims to reduce criminal recidivism among prisoners shortly awaiting release, and among probationers. Of 1,484 program participants in Sweden, 776 contained adequate data for analysis. Pre- and post-program scores were available for the Alternative Thinking Test, Levenson's Locus of Control Scale, Skill Survey, Citizen Scale, and Problem Checklist, all areas addressed in the program.

Muscle contraction induces osteogenic levels of cortical bone strain despite muscle weakness in a mouse model of Osteogenesis Imperfecta.

Mechanical interactions between muscle and bone have long been recognized as integral to bone integrity. However, few studies have directly measured these interactions within the context of musculoskeletal disease. In this study, the osteogenesis imperfecta murine model (oim/oim) was utilized because it has both reduced bone and muscle properties, allowing direct assessment of whether weakened muscle is able to engender strain on weakened bone.

High- versus low-intensity internet interventions for alcohol use disorders: results of a three-armed randomized controlled superiority trial.

Aims: To test the efficacy of a therapist-guided high-intensity internet intervention compared with an unguided low-intensity internet intervention among individuals with alcohol use disorder.

Design: A three-group randomized controlled trial with follow-up assessments post-treatment (12 weeks) and 6 months post-randomization (primary end-point).

Settings: General population sample in Sweden.

Capturing the Mechanism Underlying TOP mRNA Binding to LARP1.

The RNA-binding protein La-related protein 1 (LARP1) plays a central role in ribosome biosynthesis. Its C-terminal DM15 region binds the 7-methylguanosine (mG) cap and 5' terminal oligopyrimidine (TOP) motif characteristic of transcripts encoding ribosomal proteins and translation factors. Under the control of mammalian target of rapamycin complex 1 (mTORC1), LARP1 regulates translation of these transcripts.

Patient-Centered Outcomes in Radiation Oncology.

Patient-reported outcome and health-related quality of life scales have the potential to engage patients and providers, allowing for better communication and shared decision-making in oncology care. When monitored longitudinally, they facilitate earlier interventions that may help with symptom management and improve traditional outcome metrics, including survival. Their use in clinical trials has allowed for changes in guidelines in the management of various cancers.

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Objective: The objective of this study is to evaluate current evidence for the effectiveness of distance-based interventions to support smoking cessation (SC) or alcohol moderation (AM) among cancer survivors. Secondary, differences in effectiveness are explored regarding multibehaviour interventions versus single-behaviour interventions targeting SC or AM only.

Methods: A systematic search of PubMed, PsycINFO, Web of Science, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials was conducted.

Smartphone Apps Targeting Hazardous Drinking Patterns among University Students Show Differential Subgroup Effects over 20 Weeks: Results from a Randomized, Controlled Trial.

Overconsumption of alcohol, from hazardous to excessive, heavy, and harmful levels, is common among university students. Consenting Swedish students were assigned to one of two smartphone apps offering feedback on estimated blood alcohol concentration (eBAC; Promillekoll/PartyPlanner) or assessment only ( = 2166; 1:1:1 ratio). App participants with excessive drinking according to public health criteria (>9/>14 drinks/week for women/men, respectively) at a 7 week follow-up were additionally assigned to the skills-based TeleCoach app or waitlist ( = 186; 1:1 ratio).

Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center.

Background: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race.

Early Tumor and Nodal Response in Patients with Locally Advanced Non-Small Cell Lung Carcinoma Predict for Oncologic Outcomes in Patients Treated with Concurrent Proton Therapy and Chemotherapy.

Purpose: There are no established imaging biomarkers that predict response during chemoradiation for patients with locally advanced non-small cell lung carcinoma. At our institution, proton therapy (PT) patients undergo repeat computed tomography (CT) simulations twice during radiation. We hypothesized that tumor regression measured on these scans would separate early and late responders and that early response would translate into better outcomes.