Background In October 2020, Germany became the first country, worldwide, to approve certain mobile health (mHealth) apps, referred to as DiGA (Digitale Gesundheitsanwendungen, in German, meaning digital health applications), for prescription with costs covered by standard statutory health insurance. Yet, this option has only been used to a limited extent so far. Objective The aim of this study was to investigate physicians’ and psychotherapists’ current attitudes toward mHealth apps, barriers to adoption, and potential remedies. Methods We conducted a two-stage sequential mixed methods study. In phase one, semistructured interviews were conducted with physicians and psychotherapists for questionnaire design. In phase two, an online survey was conducted among general practitioners, physicians, and psychotherapists. Results A total of 1308 survey responses by mostly outpatient-care general practitioners, physicians, and psychotherapists from across Germany who could prescribe DiGA were recorded, making this the largest study on mHealth prescriptions to date. A total of 62.1% (807/1299) of respondents supported the opportunity to prescribe DiGA. Improved adherence (997/1294, 77.0%), health literacy (842/1294, 65.1%), and disease management (783/1294, 60.5%) were most frequently seen as benefits of DiGA. However, only 30.3% (393/1299) of respondents planned to prescribe DiGA, varying greatly by medical specialty. Professionals are still facing substantial barriers, such as insufficient information (1135/1295, 87.6%), reimbursement for DiGA-related medical services (716/1299, 55.1%), medical evidence (712/1298, 54.9%), legal uncertainties (680/1299, 52.3%), and technological uncertainties (658/1299, 50.7%). To support professionals who are unsure of prescribing DiGA, extended information campaigns (1104/1297, 85.1%) as well as recommendations from medical associations (1041/1297, 80.3%) and medical colleagues (1024/1297, 79.0%) were seen as the most impactful remedies. Conclusions To realize the benefits from DiGA through increased adoption, additional information sharing about DiGA from trusted bodies, reimbursement for DiGA-related medical services, and further medical evidence are recommended.

Adenoviruses (Ads) are large human-pathogenic double-stranded DNA (dsDNA) viruses presenting an enormous natural diversity associated with a broad variety of diseases. However, only a small fraction of adenoviruses has been explored in basic virology and biomedical research, highlighting the need to develop robust and adaptable methodologies and resources. We developed a method for high-throughput direct cloning and engineering of adenoviral genomes from different sources utilizing advanced linear-linear homologous recombination (LLHR) and linear-circular homologous recombination (LCHR). We describe 34 cloned adenoviral genomes originating from clinical samples, which were characterized by next-generation sequencing (NGS). We anticipate that this recombineering strategy and the engineered adenovirus library will provide an approach to study basic and clinical virology. High-throughput screening (HTS) of the reporter-tagged Ad library in a panel of cell lines including osteosarcoma disease-specific cell lines revealed alternative virus types with enhanced transduction and oncolysis efficiencies. This highlights the usefulness of this resource.

Background Mobile health applications and their subset digital therapeutics—defined as evidence-based software interventions to prevent, manage, or treat a medical condition—offer great potential to improve patient care. However, such solutions often struggle to reach widespread adoption. Objective This study seeks to explore healthcare stakeholders’ roles and potential for fostering patient access and adherence to evidence-based digital therapeutics and thereby improve health outcomes from the perspective of digital therapeutics developers and distributors. Methods Semi-structured qualitative and semiquantitative interviews were conducted with 19 experts from developers and distributors of digital therapeutics in Germany to discuss their perceived relevance of different healthcare stakeholders and strategies in promoting patient access and adherence to digital therapeutics. Results Healthcare professionals were found to have the greatest potential to promote both access and patient adherence to digital therapeutics, followed by health insurers, pharmaceutical companies, and patients themselves. In terms of patient access, healthcare professionals have potential due to their ability to prescribe digital therapeutics. Other stakeholders’ potential stems from their capacity to influence healthcare professionals prescription decision. In terms of patient adherence, only healthcare professionals are of high relevance by onboarding patients and monitoring digital therapeutics use. Most healthcare stakeholders currently do not fully leverage their potential. Further educating healthcare professionals and simplifying processes for them, empowering patients to seek treatment with digital therapeutics, and designing digital therapeutics’ product features for better adherence can help improve patient access and adherence. Conclusions Established healthcare stakeholders and digital therapeutics developers both need to take action to improve patient access and adherence to digital therapeutics. Several macro-level changes can support these efforts, including broader information dissemination, improved financial incentives, simplified prescription and activation processes, and a wider adoption of blended care and pay-for-performance payment models.

For efficient delivery of required genetic elements we utilized high-capacity adenoviral vectors in the past allowing high transgene capacities of up to 36 kb. Previously we explored the hyperactive Sleeping Beauty (SB) transposase (HSB5) for somatic integration from the high-capacity adenoviral vectors genome. To further improve this hybrid vector system we hypothesized that the previously described hyperactive SB transposase SB100X will result in significantly improved efficacies after transduction of target cells. Plasmid based delivery of the SB100X system revealed significantly increased integration efficiencies compared with the previously published hyperactive SB transposase HSB5. After optimizing experimental setups for high-capacity adenoviral vectors-based delivery of the SB100X system we observed up to eightfold and 100-fold increased integration efficiencies compared with the previously published hyperactive SB transposase HSB5 and the inactive transposase mSB, respectively. Furthermore, transposon copy numbers per cell were doubled with SB100X compared with HSB5 when using the identical multiplicity of infection. We believe that this improved hybrid vector system represents a valuable tool for achieving stabilized transgene expression in cycling cells and for treatment of numerous genetic disorders. Especially for in vivo approaches this improved adenoviral hybrid vector system will be advantageous because it may potentially allow reduction of the applied viral dose.

Adeno-associated virus (AAV) vectors are one of the most frequently applied gene transfer systems in research and human clinical trials. Since AAV vectors do not possess an integrase activity, application is restricted to terminally differentiated tissues if transgene expression is required long term. To overcome this limitation and to generate AAV vectors that persist episomally in dividing cells, AAV vector genomes were equipped with a scaffold/matrix attachment region (S/MAR). After a mild antibiotic selection, cells transduced with AAV-S/MAR established colonies that maintained long-term transgene expression (>50 population doublings) from replicating AAV vector episomes in the absence of further selection. Unexpectedly, with a lesser but still significant efficiency, the control vector (AAV-ΔS/MAR), a standard single-stranded AAV vector, also established stable transgene-expressing colonies, most of which were maintained as replicating episomes rather than integrated vector genomes. Thus, based on the result in HeLa cells, it is concluded that AAV vector genomes per se possess the ability to establish episomal maintenance in proliferating cells, a feature that can be enhanced by incorporation of a foreign genomic element such as an S/MAR element.