Explore the vast range of titles available.

MicroRNAs (miRNAs) are single-stranded, non-coding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and canine diseases. Most cancers tested to date have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we comprehensively summarized the importance of miRNA in human and canine cancer research. We discussed the current state of development and potential for the miRNA as both a diagnostic marker and a therapeutic target.

Five things to know about Artificial intelligence scribes in primary care are presented. 1. Artificial intelligence (AI) scribes can mimic human scribes. 2. Early evidence suggests that AI scribes lessen administrative burden and improve quality of time spent with patients. 3. Clinical documentation generated by AI scribes may contain errors and must always be reviewed. 4. Users must ensure software is compliant with local privacy regulations. 5. Users must obtain consent before using an AI scribe.

Digital tools have shown great potential to enhance health services’ capacity to achieve the goals of the triple aim (enhance patient experience, improve health outcomes, and control or reduce costs), but their actual impact remains variable. In this commentary, we suggest that shifting from a perspective focused on “implementing” new digital tools in health care settings toward one focused on “service design” will help teams execute more successful digital technology adoption projects. We present value proposition design (VPD) as a service design strategy requiring that stakeholders are brutally honest in determining the value of a new digital tool for their everyday work. Incorporating a perspective focused on how the value proposition of a technology is understood by each team member, and implications for their work routines, will help project teams to better understand how services can be reinvented during technology adoption initiatives. We present the simple heuristic [Tool+Team+Routine] as a reminder of the central considerations that make up a service design initiative, and present an illustrative case scenario of designing the use of a digital care coordination platform in an actual digital technology adoption project. We conclude by outlining two important challenges that need to be addressed to advance service design approaches to technology adoption in health care.

Virtual care use increased during the COVID-19 pandemic. The impact of that shift on patient and provider experiences is unclear. We evaluated patient and provider experiences with virtual visits across an academic, ambulatory hospital in Toronto, Canada and assessed predictors of positive experience with virtual care. During the study period, 253 patients (mean age 45.1, SD 15.6 years) completed 517 video visit surveys, and 147 patients (mean age 41.6, SD 16.4 years) completed 209 telephone visit surveys. A total of 75 and 94 providers completed the survey in June 2020 and June 2021, respectively. On a scale from 1 to 10 regarding likelihood to recommend virtual care to others, fewer providers rated a score of 8 or above compared with patients (providers: 62/94, 66% for video and 49/94, 52% for telephone; patients: 415/517, 80% for video and 150/209, 72% for telephone). Patients of non-White ethnicity had lower odds of rating a high score of 9 or 10 compared with White patients (odds ratio 0.52, 95% CI 0.28-0.99). Patient experiences with virtual care were generally positive, but provider experiences were less so. Findings suggest potential differences in patient experience by ethnicity, warranting further investigation into equity concerns with virtual care.

The COVID-19 pandemic catalyzed an uptake in virtual care. However, the rapid shift left unanswered questions about the impact of virtual care on the quality of primary care and its appropriateness and effectiveness. Moving forward, health care providers require guidance on how best to use virtual care to support high-quality primary care. This study aims to identify and summarize clinical studies and systematic reviews comparing virtual care and in-person care in primary care, with a focus on how virtual care can support key clinical functions such as triage, medical assessment and treatment, counseling, and rehabilitation in addition to the management of particular conditions. We conducted a scoping review following an established framework. Comprehensive searches were performed across the following databases: Embase, MEDLINE, PsycInfo, Emcare, and Cochrane Database of Systematic Reviews. Other well-known websites were also searched. PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines were followed. Articles were selected by considering article type, language, care provided, intervention, mode of care delivery, and sample size. A total of 13,667 articles were screened, and 219 (1.6%) articles representing 170 studies were included in the review. Of the 170 studies included, 142 (83.5%) were primary studies, and 28 (16.5%) were systematic reviews. The studies were grouped by functions of primary care, including triage (16/170, 9.4%), medical assessment and treatment of particular conditions (63/170, 37.1%), rehabilitation (17/170, 10%), and counseling (74/170, 43.5%). The studies suggested that many primary care functions could appropriately be conducted virtually. Virtual rehabilitation was comparable to in-person care and virtual counseling was found to be equally effective as in-person counseling in several contexts. Some of the studies indicated that many general primary care issues could be resolved virtually without the need for any additional follow-up, but data on diagnostic accuracy were limited. Virtual triage is clinically appropriate and led to fewer in-person visits, but overall impact on efficiency was unclear. Many studies found that virtual care was more convenient for many patients and provided care equivalent to in-person care for a range of conditions. Studies comparing appropriate antibiotic prescription between virtual and in-person care found variable impact by clinical condition. Studies on virtual chronic disease management observed variability in impact on overall disease control and clinical outcomes. Virtual care can be safe and appropriate for triage and seems equivalent to in-person care for counseling and some rehabilitation services; however, further studies are needed to determine specific contexts or medical conditions where virtual care is appropriate for diagnosis, management outcomes, and other functions of primary care. Virtual care needs to be adapted to fit a new set of patient and provider workflows to demonstrate positive impacts on experience, outcomes, and costs of care.

Cancer is the leading cause of death in the geriatric dog population. Currently, the use of immune checkpoint inhibitors (ICIs) such as anti-CTLA4 antibodies has markedly improved the prognosis of several cancers in their advanced stages. However, ICIs targeting CTLA4 blockade to treat canine cancer patients are yet to define. In this study, we sought to develop, characterize and assess whether chimeric heavy chain only antibodies (cHcAbs) against CTLA4 are viable therapeutic candidates for the treatment of canine cancers. Anti-CTLA4 nanobodies (Nbs) were identified from a yeast nanobody (Nb) library using magnetic-assisted cell sorting (MACS) and flow cytometry. cHcAbs were engineered by genetically fusing the DNA sequences coding for anti-CTLA4 Nbs with the Fc domain of the subclass B of canine IgG. Recombinant cHcAbs were purified from ExpiCHO-S cells. Stable cell lines expressing canine CTLA4 and FcγRI were used to elucidate the binding ability and specificity of cHcAbs. PBMCs isolated from healthy dogs were used to evaluate the ability of cHcAbs to activate canine PBMCs (cPBMCs). Novel Nbs were identified using the extracellular domain of canine CTLA4 protein to screen a fully synthetic yeast nanobody library. Purified Nbs bind specifically to natïve canine CTLA4. We report that chimeric HcAbs, which were engineered by fusing the anti-CTLA4 Nbs and Fc region of subclass B of canine IgG, were half the size of a conventional mAb and formed dimers. The chimeric HcAbs specifically binds both with canine CTLA4 and Fcγ receptors. As the binding of Nbs overlapped with the MYPPPY motif of canine CTLA4, these Nbs were expected to sterically disrupt the interaction of canine CTLA4 to B-7s. Like their human counterpart, canine CTLA4 was expressed on helper T cells and a small subset of cytotoxic T cells. Canine Tregs also constitutively expressed CTLA4, and stimulation with PMA/Ionomycin dramatically increased expression of CTLA4 on the cell surface. Stimulation of cPBMCs in the presence of agonistic anti-CD3 Ab and cHcAb6 significantly increased the expression of IFN-γ as compared to the isotype control. This study identifies a novel nanobody-based CTLA4 inhibitor for the treatment of canine cancer patients.

While there has been a rapid growth of digital health apps to support chronic diseases, clear standards on how to best evaluate the quality of these evolving tools are absent. This scoping review aims to synthesize the emerging field of mobile health app quality assessment by reviewing criteria used by previous studies to assess the quality of mobile apps for chronic disease management. A literature review was conducted in September 2017 for published studies that use a set of quality criteria to directly evaluate two or more patient-facing apps supporting promote chronic disease management. This resulted in 8182 citations which were reviewed by research team members, resulting in 65 articles for inclusion. An inductive coding schema to synthesize the quality criteria utilized by included articles was developed, with 40 unique quality criteria identified. Of the 43 (66%) articles that reported resources used to support criteria selection, 19 (29%) used clinical guidelines, and 10 (15%) used behavior change theory. The most commonly used criteria included the presence of user engagement or behavior change functions (97%, n  = 63) and technical features of the app such as customizability (20%, n  = 13, while Usability was assessed by 24 studies (36.9%). This study highlights the significant variation in quality criteria employed for the assessment of mobile health apps. Future methods for app evaluation will benefit from approaches that leverage the best evidence regarding the clinical impact and behavior change mechanisms while more directly reflecting patient needs when evaluating the quality of apps.

ObjectivesTo evaluate the uptake of a platform for virtual visits in primary care, examine patient and physician preferences for virtual communication methods and report on characteristics of visits and patients experience of care.DesignA retrospective cohort study.SettingPrimary care practices within five regions in Ontario, Canada after 18 months of access to virtual care services.Participants326 primary care providers and 14 291 registered patients.InterventionsProviders used a platform that allowed them to connect with their patients through synchronous (audio/video) and/or asynchronous (secure messaging) communication.Main outcome measuresUser-level data from the platforms including patient demographics, practice characteristics, communication modality used, visit characteristics and patients’ satisfaction.ResultsAmong the participants, 44% of registered patients and 60% of registered providers used the platform at least once. Among patient users, 51% completed at least one virtual visit. The majority of virtual visits (94%) involved secure messaging. The most common patient requests were for medication prescriptions (24%) and follow-up from previous appointment (22%). The most common provider request was to follow-up on test results (59%). Providers indicated that 81% of virtual visits required no follow-up for that issue and 99% of patients reported that they would use virtual care services again.ConclusionsWhile there are a growing number of primary care video visit services, our study found that both patients and providers in rostered practices prefer secure messaging over video. Despite fears that virtual visits would be overused by patients, when patients connected with their own primary care provider, many virtual visits appeared to replace in-person visits, and patients did not overwhelm physicians with requests. This approach may improve access and continuity in primary care.

PurposeWe sought to understand patients’ care-seeking behaviours early in the pandemic, their use and views of different virtual care modalities, and whether these differed by sociodemographic factors.MethodsWe conducted a multisite cross-sectional patient experience survey at 13 academic primary care teaching practices between May and June 2020. An anonymised link to an electronic survey was sent to a subset of patients with a valid email address on file; sampling was based on birth month. For each question, the proportion of respondents who selected each response was calculated, followed by a comparison by sociodemographic characteristics using χ2 tests.ResultsIn total, 7532 participants responded to the survey. Most received care from their primary care clinic during the pandemic (67.7%, 5068/7482), the majority via phone (82.5%, 4195/5086). Among those who received care, 30.53% (1509/4943) stated that they delayed seeking care because of the pandemic. Most participants reported a high degree of comfort with phone (92.4%, 3824/4139), video (95.2%, 238/250) and email or messaging (91.3%, 794/870). However, those reporting difficulty making ends meet, poor or fair health and arriving in Canada in the last 10 years reported lower levels of comfort with virtual care and fewer wanted their practice to continue offering virtual options after the pandemic.ConclusionsOur study suggests that newcomers, people living with a lower income and those reporting poor or fair health have a stronger preference and comfort for in-person primary care. Further research should explore potential barriers to virtual care and how these could be addressed.

Genetically modified oncolytic adenoviruses have been proposed as a vehicle for cancer therapy. However, several concerns, such as toxicity to normal cells and organs, lack of suitable cell surface receptors to allow viral entry to the desired cell type(s), and activation of both innate and adaptive immune systems in patients, restrict the successful clinical application of adenoviral-mediated cancer gene therapy. Successful virotherapy will require efficient transductional and transcriptional targeting to enhance therapeutic efficacy by ensuring targeted adenoviral infection, replication, and/or therapeutic transgene expression. Targeted modification of viral components, such as viral capsid, fiber knob, and the insertion of transgenes for expression, are prerequisites for the necessary transductional and transcriptional targeting of adenovirus. However, the conventional approach to modify the adenoviral genome is complex, time consuming, and expensive. It is dependent on the presence of unique restriction enzyme sites that may or may not be present in the target location. Clustered regularly interspaced short palindromic repeat (CRISPR) along with the RNA-guided nuclease Cas9 (CRISPR/Cas9) is one of the most powerful tools that has been adopted for precise genome editing in a variety of cells and organisms. However, the ability of the CRISPR/Cas9 system to precisely and efficiently make genetic modification, as well as introduce gene replacements, in adenoviral genomes, remains essentially unknown. Herein the ability of in vitro CRISPR/CAS9-mediated editing of the canine adenovirus type 2 (CAV2) genome to promote targeted modification of the viral genome was assessed. To demonstrate the feasibility of this goal, CRISPR/Cas9 has been used to successfully insert the RFP (red fluorescent protein) reporter construct into the CAV2 genome. Initial results demonstrated high efficiency and accuracy for in vitro CRISPR-mediated editing of the large CAV2 genome. Furthermore, this application was expanded, using multiple guide RNAs, to conduct gene replacement in the CAV2 genome by substituting a portion of the E3 gene with a construct designed to express a single chain antibody to canine PD-1. Thus, this work provides a significantly improved and efficient method for targeted editing of adenoviruses to generate altered and potentially therapeutic viral genomes in the shortest possible time.