Radically different
Nature Medicine, Published online: 13 July 2026; doi:10.1038/s41591-026-04570-9
Author Correction: The STARD-AI reporting guideline for diagnostic accuracy studies using artificial intelligence
A new genome-scale atlas is offering an unprecedented look at how individual genes shape the transcriptional landscape of human induced pluripotent stem cells (iPSCs). Published in Nature Biotechnology, the resource catalogs the effects of perturbing 11,692 expressed genes across more than 2.5 million single cells, creating a reference framework for understanding how pluripotent identity is maintained and regulated.
The study is titled, “A genome-scale CRISPRi perturbation atlas of human induced pluripotent stem cells.”
Human iPSCs can differentiate into virtually any cell type, yet the functions of most genes within this state remain poorly understood. Prashant Mali, PhD, senior author and professor of bioengineering at UC San Diego, said the team set out to fill that gap by systematically switching off genes one by one using CRISPR interference (CRISPRi) and measuring the resulting transcriptome-wide changes. “The result is a kind of reference atlas; it’s a way to look up what perturbing almost any gene does to a stem cell’s behavior, measured here as the impact on its whole transcriptome,” Mali said.
The dataset captures how gene perturbations cluster into shared molecular signatures, revealing functional relationships among protein complexes, metabolic pathways, and self-renewal genes. By correlating transcriptional phenotypes across thousands of perturbations, the researchers reconstructed a map of the pluripotent state that recapitulates known regulatory modules while surfacing previously unrecognized ones.
Exploring the atlas led the team to identify new regulators of stem cell biology. They uncovered ZBTB41 as a metabolic factor and RNF7 as a contributor to pluripotency regulation, validating both through metabolic tracing, immunofluorescence, and protein–protein interaction assays. The resource also enabled a genome-scale screen of A‑to‑I RNA editing modulators, revealing DBR1 as a potent regulator of adenosine-to-inosine conversion.
Co-first author Yesh Doctor, a bioengineering PhD student in Mali’s lab, described the atlas as a “hypothesis engine” for stem cell researchers. Instead of running thousands of perturbation experiments, scientists can now query the open-access map to identify candidate genes involved in differentiation, metabolism, or disease-relevant pathways. “Scientists can use it to look up the functions of genes and build hypotheses on them instead of having to run the experiments themselves,” Doctor said.
Beyond basic biology, the team sees the atlas as a foundation for computational modeling. The scale and consistency of the dataset make it well suited for training AI systems aimed at predicting genotype–phenotype relationships. “These comprehensive, genome-scale screens enable generation of reference maps that are not just invaluable for basic science discovery, but also an important resource for powering future computational and AI tools for genotype-phenotype prediction,” Mali said.
The open-access atlas is available here, providing a new reference point for understanding how genes shape human stem cell identity and offering a tool for virtual disease modeling and target discovery.
The post Genome-Scale CRISPRi Atlas Maps Gene Function Across Human iPSCs appeared first on GEN – Genetic Engineering and Biotechnology News.
Background: Serious games are increasingly used in professional health education and maternal health promotion. However, most pregnancy-related digital interventions target specific behaviors and do not provide a comprehensive, longitudinal simulation of the pregnancy journey that incorporates psychosocial and administrative aspects. Objective: This study aimed to develop and evaluate a narrative-based serious game that simulates the chronological course of pregnancy and to assess its perceived educational usefulness, accessibility, and user acceptance across multiple platforms. Methods: We developed a 9-chapter interactive serious game covering pregnancy recognition, partner communication, public health consultation, mid-pregnancy and late-pregnancy checkups, and home preparation for childbirth. The game was collaboratively created by a pediatrician, 6 medical students, and a student illustrator using a low-cost visual novel engine (TyranoBuilder). It was released in April 2025 on iOS, Android, and Steam. A voluntary, anonymous postgame survey was conducted between April 2025 and January 2026. Descriptive statistics were used to summarize survey responses and platform analytics. This study was approved by the Ethics Committee of Shinshu University Hospital. Results: A total of 65 users completed the postgame questionnaire. Most respondents were aged 10 to 19 years (38/65, 58.5%) and female (55/65, 84.6%). Nearly half of the participants (30/65, 46.2%) completed the game within 1 hour. Gameplay evaluation scores (5-point Likert scale; 3=neutral or appropriate) were balanced: game length (mean 3.37, SD 0.96), difficulty (mean 2.84, SD 0.85), and interactivity (mean 3.31, SD 1.10). Educational outcomes were rated highly (5-point Likert scale; higher=more favorable): reduced anxiety (mean 3.84, SD 0.96), perceived educational usefulness (mean 3.98, SD 1.02), perceived knowledge acquisition (mean 4.06, SD 1.06), story empathy (mean 3.80, SD 1.11), and overall satisfaction (mean 4.05, SD 1.04). Across all platforms, the game achieved 925 cumulative downloads. iOS and Android downloads were predominantly from Japan, whereas Steam downloads were geographically diverse. Of the 21 Steam reviews, 20 (95.2%) were positive. Conclusions: A serious pregnancy education game developed through a low-cost clinician-student collaborative model demonstrated high perceived educational usefulness, balanced gameplay characteristics, and broad user acceptance, including substantial engagement among teenagers and international users. Narrative-based serious games represent an accessible and scalable approach to maternal health education. Further research using more rigorous evaluation designs is warranted to assess long-term educational and behavioral impacts.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/e2f36ab34de77d0bdb26718b9c29b61f" />
Background: mWorks is a co-designed, web-based self-management intervention developed to empower persons with common mental disorders who are on sick leave during the return-to-work process. However, limited knowledge of how mWorks is delivered and engaged with in real-world settings constrains further development and implementation. In line with the Medical Research Council framework for complex intervention evaluation, such an approach is required to examine (1) contextual factors influencing implementation, (2) fidelity and variation in delivery, and (3) how service users and professionals experience and respond to the intervention. Objective: This study aimed to evaluate the process of implementing mWorks, specifically focusing on assessing the intervention’s delivery in relation to the context, implementation process, and mechanisms of impact. Methods: This single-case study was bounded by the delivery period of 10 weeks in a primary and specialist mental health service context. During this period, return-to-work professionals (n=2) and service users (n=6) collaborated to initiate mWorks usage. Both qualitative and quantitative methods were used to triangulate multiple data sources. Results: The pandemic and mental health problems posed contextual barriers, particularly during recruitment. However, perceptions of mWorks as a credible and relevant intervention facilitated its implementation. The delivery was performed according to plan, with minimal adaptations. All users adhered to the intervention, and dialogue meetings were highly valued. mWorks was used flexibly according to users’ needs, both during sick leave and at work. The potential impacts included a transformative process for users, fostering acceptance, self-esteem, self-compassion, and a sense of control. It also had the potential to prevent mental ill health, transform negatives into positives, facilitate disclosure of mental health, and support goal setting. The use of quantitative measures for empowerment, engagement, self-efficacy, depression stigma, and quality of life proved feasible and supported the assumptions and direction of results. Conclusions: The recruitment stage of the implementation program encountered significant contextual barriers. However, once the delivery stage began, the implementation of mWorks proved to be feasible. Despite the limited scope of this study, with its small number of participants, the triangulation of data suggests that both users and professionals benefited from mWorks.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/0f2e619d10828588de6867489083472e" />
Background: Remote measurement technology (RMT) is increasingly used in health research to collect real-world data relevant to clinical states (eg, sleep, activity, and stress). Concerns exist about the impact of remote tracking via personal devices and wearables on individuals with or at risk of eating disorders (EDs) by promoting a focus on exercise, diet, and appearance. There is a lack of research applying RMT to EDs. Objective: This study aimed to explore how smartphone- and wearable-based RMTs influence eating-, exercise-, and weight-related experiences among individuals with a history of or at risk of EDs and to identify perceived benefits, harms, and recommendations for their use in this population. Methods: In total, 14 semistructured interviews were conducted with former participants of Remote Assessment of Disease and Relapse: Major Depressive Disorder, a 2-year digital health study tracking depression outcomes via RMTs. Participants were included in this follow-up if they had disclosed a history of a comorbid ED or were within the at-risk age range (18-30 years) for EDs during Remote Assessment of Disease and Relapse: Major Depressive Disorder and displayed subclinical ED symptoms (Eating Disorder Diagnostic Scale). Interviews explored the impact of app engagement and wearables (Fitbits) on food, activity, and weight-related behaviors and attitudes. Template analysis was adopted to capture themes guided by the focus on ED-relevant domains. Results: In total, 6 themes captured participants’ experiences with RMTs across clinical status and presentation. Participants broadly appreciated the convenience and reflective potential, while some described emotional strain linked to constant self-tracking. Health data impacted participants’ eating and exercise habits through a dynamic process from awareness to cognition to action, fostering healthy routines or obsessive patterns, depending on emotional state, ED presentation, and recovery stage. Self-tracking appeared to mirror illness stage, supporting ED recovery among those with greater distance from illness, but risking reinforcement of compulsive patterns among those with residual or emerging symptoms. Participants’ recommendations for future studies in EDs stressed balancing autonomy with safeguards for vulnerable individuals. Conclusions: These exploratory findings, drawn from individuals with lived ED experience and young people at subclinical risk, suggest that RMT use was shaped by recovery stage and contextual factors, rather than being inherently beneficial or harmful. While findings should not be interpreted as evidence of RMT safety or acceptability in ED cohorts broadly, they raise important questions about ethical RMT design, including the selection of wearables, access to data, and researcher communication with participants.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/b169595d201412fcf0e45228d9bad465" />
A large study of people with type 2 diabetes suggests that those who started treatment with a glucagon‑like peptide (GLP)‑1 receptor agonist after diagnosis had slightly increased risk of developing a serious eye condition called ischemic optic neuropathy than people with diabetes treated with other medications.
As reported in the Annals of Internal Medicine, the risk for patients given GLP-1 drugs was about twice that of those given a sodium–glucose cotransporter (SGLT)‑2 inhibitor or a dipeptidyl peptidase (DPP)-4 inhibitor although the absolute risk was still low in all groups.
Ischemic optic neuropathy occurs when the optic nerve sustains damage caused by reduced or blocked blood flow, leading to loss of nerve tissue and vision. The main symptom is sudden, usually painless vision loss in one eye, often with missing areas of the visual field that are frequently permanent. It is a rare condition, with 4-10 cases per 100,000 people per year in the U.S., with some factors like age and conditions like type 2 diabetes increasing risk.
In this study, Chintan Dave, PhD, a researcher at Rutgers University, and colleagues included claims data from 161,489 adults aged 18 to 65 years with type 2 diabetes who were newly prescribed a GLP-1 receptor agonist, 122,114 who started a SGLT‑2 inhibitor, and 86,047 who started a DPP‑4 inhibitor.
They excluded anyone who had previously used these drugs or previously had ischemic optic neuropathy. They approximated randomization by balancing more than 80 characteristics across groups. They then collected follow up data for up to 18 months to see who was later diagnosed with ischemic optic neuropathy.
Over 18 months, about nine out of every 10,000 people in the GLP-1 group were diagnosed with ischemic optic neuropathy, compared with about six out of 10,000 in the GLT‑2 inhibitor group and about four out of 10,000 in the DPP‑4 inhibitor group. Essentially there were three to four extra cases of ischemic optic neuropathy per 10,000 patients in the GLP-1 compared with the other groups.
The researchers note that the apparent excess risk was concentrated in older adults, men, and people with more advanced diabetes or eye or cardiovascular conditions.
GLP-1 receptor agonists are now widely used, both in lower doses for treatment of type 2 diabetes and in higher doses to treat obesity. “Despite the very low absolute risk for ischemic optic neuropathy, the rapidly expanding use of GLP-1 receptor agonists in patients with and without type 2 diabetes increases the clinical and public health importance of any potential association,” conclude the authors.
“Given that type 2 diabetes itself is a risk factor for nonarteritic anterior ischemic optic neuropathy [which constitutes approximately 75% of ischemic optic neuropathy cases] the potential for GLP-1 receptor agonists to further augment this risk has relevant implications for clinical decision making.”
The post GLP-1 Treated Patients with Diabetes Have Raised Risk for Eye Condition appeared first on Inside Precision Medicine.