Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Newly Qualified Canadian Nurses' Experiences With Digital Health in the Workplace: Comparative Qualitative Analysis.

Background: Clinical practice settings have increasingly become dependent on the use of digital or eHealth technologies such as electronic health records. It is vitally important to support nurses in adapting to digitalized health care systems; however, little is known about nursing graduates' experiences as they transition to the workplace.

Objective: This study aims to (1) describe newly qualified nurses' experiences with digital health in the workplace, and (2) identify strategies that could help support new graduates' transition and practice with digital health.

Resources to Support Canadian Nurses to Deliver Virtual Care: Environmental Scan.

Background: Regulatory and professional nursing associations have an important role in ensuring that nurses provide safe, competent, and ethical care and are capable of adapting to emerging phenomena that influence society and population health needs. Telehealth and more recently virtual care are 2 digital health modalities that have gained momentum during the COVID-19 pandemic. Telehealth refers to telecommunications and digital communication technologies used to deliver health care, support health care provider and patient education, and facilitate self-care.

Digital Health Education and Training for Undergraduate and Graduate Nursing Students: Scoping Review.

Background: As technology will continue to play a pivotal role in modern-day health care and given the potential impact on the nursing profession, it is vitally important to examine the types and features of digital health education in nursing so that graduates are better equipped with the necessary knowledge and skills needed to provide safe and quality nursing care and to keep abreast of the rapidly evolving technological revolution.

Objective: In this scoping review, we aimed to examine and report on available evidence about digital health education and training interventions for nursing students at the undergraduate and graduate levels.

Methods: This scoping review was conducted using the Joanna Briggs Institute methodological framework and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews).

Time-efficient germ cell transplantation from goldfish () into adult common carp ().

Germ cell transplantation in fish is a promising technique for surrogate broodstock parents with broader application in aquaculture and conserving endangered and valuable genetic resources. Herein, we describe the establishment of an intrapapillary xenogeneic transplant of germ cells from sexually mature goldfish () males into common carp () males cytoablated with a thermochemical treatment (two doses of busulfan at 40 mg/kg at 35°C). To analyze the presence and development of donor germ cells in recipient testes, donor germ cells were labeled with PKH26, a fluorescent cell membrane dye, before transplantation.

Acceptance of the Apple Watch Series 6 for Telemonitoring of Older Adults With Chronic Obstructive Pulmonary Disease: Qualitative Descriptive Study Part 1.

Background: The Apple Watch is not a medical device per se; it is a smart wearable device that is increasingly being used for health monitoring. Evidence exists that the Apple Watch Series 6 can reliably measure blood oxygen saturation (SpO) in patients with chronic obstructive pulmonary disease under controlled circumstances.

Objective: This study aimed to better understand older adults' acceptance of the Watch as a part of telemonitoring, even with these advancements.

Experiences of Patients With Chronic Obstructive Pulmonary Disease Using the Apple Watch Series 6 Versus the Traditional Finger Pulse Oximeter for Home SpO2 Self-Monitoring: Qualitative Study Part 2.

Background: Amid the rise in mobile health, the Apple Watch now has the capability to measure peripheral blood oxygen saturation (SpO). Although the company indicated that the Watch is not a medical device, evidence suggests that SpO measurements among patients with chronic obstructive pulmonary disease (COPD) are accurate in controlled settings. Yet, to our knowledge, the SpO function has not been validated for patients with COPD in naturalistic settings.

Digital health education and training for undergraduate and graduate nursing students: a scoping review protocol.

Objective: The objective of this review is to collate and analyze literature reporting on digital health education and training courses, or other pedagogical interventions, for nursing students at the undergraduate and graduate level to identify gaps and inform the development of future educational interventions.

Introduction: In this era of technology-driven health care, upskilling and/or reskilling the nursing workforce is urgently needed for nurses to lead the digital health future and improve patient care. While informatics competency frameworks serve to inform nursing education and practice, they do not address the entire digital health spectrum.

Cannabidiol improves Nile tilapia cichlid fish welfare.

Cannabidiol (CBD) is a substance derived from Cannabis sativa, widely studied in medicine for controlling neural diseases in humans. Besides the positive effects on humans, it also presents anxiolytic proprieties and decreases aggressiveness and stress in mammals. Therefore, CBD has the potential to increase welfare in reared animals, as it seems to reduce negative states commonly experienced in artificial environments.

Study of Acetylcholinesterase and Beta-secretase Inhibitors: Potential Multitarget Anti-Alzheimer's Agents.

Background: Alzheimer's disease is a progressive neurodegenerative process with multifactorial characteristics. This disease follows the natural aging process, affecting mainly people over 65 years. Pharmacotherapeutic treatment currently combats symptoms related to cognitive function.

Efficient Spectrum Occupancy Prediction Exploiting Multidimensional Correlations through Composite 2D-LSTM Models.

In cognitive radio systems, identifying spectrum opportunities is fundamental to efficiently use the spectrum. Spectrum occupancy prediction is a convenient way of revealing opportunities based on previous occupancies. Studies have demonstrated that usage of the spectrum has a high correlation over multidimensions, which includes time, frequency, and space.

Effects of Rovalpituzumab Tesirine on Ventricular Repolarization in Patients With Small-Cell Lung Cancer.

Small cell lung cancer (SCLC) is a leading cause of cancer death worldwide, with few treatment options. Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate that targets delta-like 3 on SCLC cells to deliver a cytotoxic payload directly to tumor cells. In this study, the cardiac safety profile of Rova-T was assessed by evaluating changes in QT interval, electrocardiogram (ECG) waveform, heart rate, and proarrhythmic adverse events (AEs) after treatment with Rova-T in patients with previously treated extensive-stage SCLC.

Epigenetic priming by EHMT1/EHMT2 in acute lymphoblastic leukemia induces TP53 and TP73 overexpression and promotes cell death.

Euchromatic histone-lysine N-methyltransferase 1 (EHMT1) and EHMT2 are upregulated in various human cancers, and their deregulation is associated with tumor development and progression. In this paper, we investigated the expression level of EHMT1/EHMT2 in acute lymphoblastic leukemia (ALL) and whether the modulation of these enzymes could have any cellular or molecular impact on ALL cells. For this, we used UNC0646 as a priming strategy to target EHMT1/EHMT2 and investigated its effect on proliferation and cell viability of Jurkat cells by MTT assay.

Clonal Decomposition and DNA Replication States Defined by Scaled Single-Cell Genome Sequencing.

Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material.

A narrative review on the consultation tools available for pharmacists in the United Kingdom: do they facilitate person-centred care?

Objectives: To identify consultation tools cited in the published literature and undertake a narrative review which establishes their scope to support the delivery of person-centred medicine-focused consultations between community pharmacists and patients in the United Kingdom (UK).

Key Findings: Nine consultation tools used in a pharmacy context were identified. Four tools (Calgary-Cambridge guide, MRCF, MUR and NMS advanced services and PaCT) were selected for further appraisal.

A single-center, open-label study investigating the excretion balance, pharmacokinetics, metabolism, and absolute bioavailability of a single oral dose of [C]-labeled idasanutlin and an intravenous tracer dose of [C]-labeled idasanutlin in a single cohort of patients with solid tumors.

Purpose: Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic p53 activator with oral administration. To determine the need to conduct dedicated trial(s) for organ impairment on pharmacokinetic (PK) exposure and/or drug-drug interactions, a single dose of [C]- and [C]-labeled idasanutlin was evaluated.

Methods: This study was an open-label, non-randomized, single-center trial of idasanutlin to investigate the excretion balance, pharmacokinetics, metabolism, and absolute bioavailability of a single oral dose of [C]-labeled idasanutlin and an IV tracer dose of [C]-labeled idasanutlin in a single cohort of patients with solid tumors.

Development of a tool to support person-centred medicine-focused consultations with stroke survivors.

Objective: To develop a tool to support medicine-focused person-centred consultations between community pharmacists and stroke survivors.

Method: Semi-structured interviews with 15 stroke survivors and 16 community pharmacists were conducted. Thematic analysis of the data was performed and emerging themes examined to determine their relevance to the principles of delivering person-centred care.

[Helicobacter pylori infection detected during upper gastrointestinal endoscopy].

Background: Helicobacter pylori (HP) is the most widespread chronic human infection worldwide and the most important pathogenic factor of gastric cancer. The calculated prevalence at the Clinical Hospital of the University of Chile from 2002 to 2005 was 44.9%.

[Fundal variceal bleeding treated with balloon occluded endoscopic inyection sclerotherapy. Report of two cases].

Management of gastrointestinal bleeding caused by fundal varices is particularly difficult to manage. The options are: transjugular intrahepatic portosystemic shunt (TIPS), endoscopic injection of cyanoacrylate or balloon-occluded retrograde transvenous obliteration (BRTO). We report a 63 year-old male with a cirrhosis caused by hepatitis C and a 66 year-old female with a cirrhosis caused by a non-alcoholic steatohepatitis.

The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2'-α-chloro-2'-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors.

Herein we describe the discovery of IDX21437 35b, a novel Rd-aminoacid-based phosphoramidate prodrug of 2'-α-chloro-2'-β-C-methyluridine monophosphate. Its corresponding triphosphate 6 is a potent inhibitor of the HCV NS5B RNA-dependent RNA polymerase (RdRp). Despite showing very weak activity in the in vitro Huh-7 cell based HCV replicon assay, 35b demonstrated high levels of active triphosphate 6 in mouse liver and human hepatocytes.

Discovery of benzophosphadiazine drug candidate IDX375: A novel hepatitis C allosteric NS5B RdRp inhibitor.

Hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp) plays a central role in virus replication. NS5B has no functional equivalent in mammalian cells, and as a consequence is an attractive target for selective inhibition. This paper describes the discovery of a novel family of HCV NS5B non-nucleoside inhibitors inspired by the bioisosterism between sulfonamide and phosphonamide.