The Associated Press Stylebook, the foundational journalism guide for how newsrooms report and write their stories, made waves last week when it decreed that “health care” should now be written as one word, not two. The change, announced at the annual ACES: The Society for Editing’s conference, was prompted by shifting usage and years of appeals to make the switch.
STAT closely follows AP style and has used “health care” since its founding in 2015. Now, we have to decide whether to adopt this new guidance, but our newsroom is divided.
Background: Digital self-control tools (DSCTs) have emerged as technological interventions to address excessive smartphone usage and promote digital well-being. However, these tools face persistent challenges with user attrition and sustained engagement, compromising their long-term effectiveness. Current literature lacks an understanding of how observable behavioral indicators, as opposed to self-reported measures, are associated with user engagement and readiness to change in DSCTs. Objective: This study addresses three research questions (RQs): (RQ1) whether prompting passive DSCT users to reconfigure nudges increases subsequent user-nudge interaction, (RQ2) how engagement evolves over time and what behavioral divergence emerges between accepting and rejecting users, and (RQ3) whether observable in-app behavioral indicators are more strongly associated with intervention acceptance than traditional self-reported measures. Methods: We conducted a quasi-experimental study (N=252) targeting users who had disabled nudges. Participants were randomly assigned to receive a prompt to reconfigure their nudge settings during daily check-ins (n=138, experimental group) or to a control condition (n=114, no intervention). The experimental group was further classified into acceptance and rejection subgroups based on their response to the intervention. Data collection included DSCT configuration logs, usage-triggered nudge logs, and self-reported questionnaire responses. We analyzed user-nudge interaction ratios using difference-in-differences with permutation tests (RQ1) and nudge configuration parameters and manual app blocking using independent-samples tests with Cohen (RQ2) and compared behavioral indicators against self-reported measures using tests and chi-square tests (RQ3). Results: Of the experimental participants, 46% (63/138) accepted the nudge reconfiguration prompt. Post intervention, the acceptance subgroup’s 7-day average user-nudge interaction ratio increased from 29.7% to 58.5% (peak of 65% on day 1), a significant increase even after controlling for the temporal decline observed in the control group (difference-in-differences=+36.3 percentage points, <.001). The rejection subgroup’s decline was not significantly different from the control group’s decline (=.82). The acceptance subgroup showed preexisting behavioral indicators of higher readiness to change, including 21.53% shorter consecutive usage thresholds (=.03) compared to the rejection subgroup, with a directionally consistent but nonsignificant difference in cooldown length (+20.56%). Behavioral divergence in consecutive usage thresholds widened post intervention, with Cohen increasing from −0.47 to −0.67 (=.002). Acceptance subgroup participants demonstrated a significantly lower tendency to select leisure-oriented daily goals (15.6% vs 26.2%; chi-square =.001, Cramer =0.13). Self-reported measures of screen time goals and scrolling regret were not significantly associated with intervention acceptance (>.10). Conclusions: Observable in-app behavioral indicators, rather than self-reported measures, effectively differentiate intervention receptiveness. Study results suggest that effective DSCT design should incorporate adaptive strategies that recognize and respond to users’ readiness to change, as evidenced by their in-app behaviors, while preserving autonomy. Such systems are likely to outperform static interventions or designs that rely solely on self-reported preferences.
Why does it take a new drug 10 years, on average, to come to market? Part of the reason lies in the dead time in the process.
Historically, trials have required tedious tabulations and repeated application submissions between phases, which is why 45% of the time from a Phase 1 trial until final submission is spent without any ongoing clinical trial in progress — idle time in the system.
What happens when the scalability and redosability of messenger RNA (mRNA) is combined with the durability and programmability of gene therapy?
According to Serif Biomedicines, a five-year-old startup that emerged from stealth mode this month, the result is “modified DNA,” a new class of therapeutics designed to be programmable, durable, scalable, and redosable—while minimizing the drawbacks of both mRNA and gene therapy.
Modified DNA builds upon generative protein and mRNA platforms created by Flagship Pioneering, the venture capital giant which founded Serif in 2021. On April 21, Flagship formally launched Serif with an initial commitment of $50 million in financing—capital that Serif intends to use toward developing its scalable platform for optimizing and manufacturing Modified DNA treatments, aided by artificial intelligence (AI), and advancing its first drug discovery programs.
“The reason we’re bringing the company out of stealth mode now is we think we have made progress. We’ve made real progress that we’re excited to share with the world, that we’re excited to get feedback from the broader scientific community on, and we want to tell that story more broadly,” Jacob (Jake) Rubens, PhD, Serif’s co-founder and CEO, and an Origination Partner at Flagship Pioneering, told GEN.
“It’s been on our minds for a long time: What might be possible when DNA becomes an engineerable biotechnology for the first time?”
It’s a question pursued by numerous researchers and companies over the years as they sought to capitalize on DNA’s qualities of being a durably expressing molecule capable of coding for any gene, producing proteins or RNAs in a cell-specific way, as well as being scalable to manufacture and capable of re-dosing for patients.
“Those are, I think, the key differentiating attributes of theoretical DNA medicines. So the question for us became not, would this be valuable if we could do it, but why hasn’t anyone done it yet?” Rubens explained. “We’ve known about the centrality of DNA in biology, the central information molecule in DNA. We’ve known this for 75 years since Watson and Crick’s seminal discoveries around how the structure of DNA enabled it to function as an information molecule.”
Two key problems
Jacob (Jake) Rubens, PhD, Serif Biomedicines co-founder and CEO
“And when we looked at this space,” he continued, “we saw that there were two key problems: The first is that DNA is a highly inflammatory molecule. The second is that DNA needs to be delivered not just into a cell, but into the nucleus, the center of the cell.”
To create Modified DNA, Serif alters the structural and chemical form of DNA in order to minimize innate immunogenicity as lipid nanoparticles drop off the DNA not in the nucleus, but in the cytoplasm of the cell.
Once inside the cell nucleus, Modified DNA reverts to unmodified DNA, enabling transcription into therapeutic RNA and proteins. The resulting treatments are designed to last longer, be given more than once, and be programmed for cell-specific expression. To enhance durability, Serif delivers with its Modified DNA proteins which help the DNA access the nucleus. The proteins, called mRNA co-factors, are designed to transiently express proteins that enhance entry into the nucleus and gene expression.
Pending an announcement it expects to make later this year, Serif isn’t revealing specifics of its initial drug discovery programs, except to say that they focus on rare diseases and immune programming.
“This is not meant to be a limited list of where we could go but the areas that we think we’re going to go first, which are likely in addressing protein deficiencies in genetic diseases,” Rubens said.
Modified DNA has shown itself to be disease agnostic, he added, reflecting DNA’s qualities as a general, programmable information molecule: “One of the reasons we’re so excited about, the future of modified DNA as a new biotechnology akin to RNA, akin to protein, is its centrality in biology. It is the fundamental information molecule inside of all of us, inside of every living thing on this planet. So that is really the existence proof that it is generalizable.”
Tolerability and sustained expression
Also later this year, Serif plans to present data at an as-yet-unspecified scientific conference that will show modified DNA’s tolerability in non-human primates, as well as sustained gene expression with therapeutic effects in preclinical models following intravenous (IV) administration.
Serif aims to transform Modified DNA into treatments as effectively and commercially successfully as Amgen, Genentech (now a member of the Roche Group), and later Regeneron did with engineered proteins, as Alnylam Pharmaceuticals did with small interfering RNA (siRNA), and as Moderna more recently accomplished with mRNA—most notably in developing its SpikeVax® COVID-19 vaccine, which the FDA authorized for emergency use in 2020 and fully approved in 2022.
Flagship launched Moderna in 2010; the company went public in 2018 by raising $604 million, the largest-ever U.S. biotech initial public offering (IPO) until Kailera Therapeutics raised $625 million earlier this month.
At Flagship, Rubens is a scientist entrepreneur who leads the firm’s Pioneering Business Unit, which establishes and grows companies based on new biotechnology. In addition to Serif, Rubens co-founded Quotient Therapeutics, which develops therapies based on its somatic genomics platform; Tessera Therapeutics, which writes therapeutic messages into the genome through a genome engineering approach called GeneWriting; and Sana Biotechnology, a developer of treatments based on engineered cells. He also launched Kaleido Biosciences, a microbiome therapeutics company that ceased operations in 2022.
Before joining Flagship, Jake received his PhD in microbiology from MIT, working with Tim Lu, MD, PhD, a core member of the Synthetic Biology Center, through the support of a National Science Foundation Graduate Research Fellowship. At MIT, Jake helped enable “intelligent” cell therapies by inventing gene circuits that allow engineered cells to do novel analog, digital, and hybrid computations.
Based in Cambridge, MA, Serif employs about 50 people and as of Wednesday was disclosing five open positions on its website in its three areas of focus: Chemistry (associate scientist and senior scientist, both specializing in LNP formulations), Molecular Biology (research associate and senior scientist), and Research/Discovery (scientist specializing in bioanalytical assays).
“I’m not at this point going to provide any guidance on how much more we will or won’t grow,” Rubens said. “We’re quite agile and responsive to the company’s needs.”
<![CDATA[AI video screening spots early tardive dyskinesia signs, prompting clinical follow-up and treatment.]]>
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<![CDATA[Read our exclusive interview with Daniel R. Karlin, MD, MA, on the latest executive order, DT120 for the treatment of mental health disorders, and more.]]>
Background: In October 2022, the Nutrition Now (NN) e-learning resource was implemented within Maternal and Child Healthcare centers and Early Childhood Education and Care centers of a southern Norwegian municipality. The e-learning resource targets expectant parents, parents of children aged 0‐2 years, and Early Childhood Education and Care staff, aiming to promote healthy dietary behaviors during the first 1000 days of life. Objective: This study aimed to explore parental perceptions related to the acceptability, appropriateness, feasibility, and reported use of the NN e-learning resource among parents. Methods: From October 2022 to May 2023, expecting parents and parents of children aged 0‐2 years were recruited from 2 Norwegian municipalities, one intervention group receiving access to the NN e-learning resource, and one control. Participants in the intervention group received a web-based follow-up questionnaire 7 months after gaining access to the NN e-learning resource. Data were analyzed using descriptive statistics. Results: Of the 179 participants in the NN study intervention group, 48 completed the web-based follow-up questionnaire administered 7 months after enrollment. Parents rated the e-learning resource positively on items assessing whether they liked and appreciated the resource, perceived it as an appropriate source of information, and found it doable and easy to use. Most respondents reported visiting the resource (38/48, 79%), although only 21% (10/48) reported frequent visits. Less than half of the participants answering the web-based follow-up questionnaire reported having watched the theme films (20/48, 42%), the recipe films (17/48, 35%), or making food using recipes provided in the e-learning resource (20/48, 42%). Conclusions: Parents rated the NN e-learning resource positively but reported limited use. These findings point to the need for strategies that enhance engagement with self-guided digital interventions among expectant parents and parents of young children. Future efforts should focus on identifying how to maximize potential adoption of the e-learning resource and evaluate its impact to promote healthy dietary behaviors during the first 1000 days of life. Trial Registration: ISRCTN Registry ISRCTN10694967; https://www.isrctn.com/ISRCTN10694967
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<![CDATA[Spot ICU delirium early with MD‑MOSAIC—an exam for ventilated patients that sharpens diagnosis, prevents harm, and improves outcomes.]]>
In a new study published in Nature Signal Transduction and Targeted Therapy titled, “Drugging the intrinsically disordered transactivation domain of androgen receptor,” researchers from the University of British Columbia and BC Cancer present a new approach for designing drugs that bind more strongly to intrinsically disordered proteins. These proteins play a central role in a wide range of diseases, including cancer, neurodegenerative disorders, heart disease and autoimmune conditions, and are extremely difficult to target due to their flexible nature.
Transactivation domains (TADs) of transcription factors are enriched in intrinsically disordered regions (IDRs) that lack a stable three-dimensional structure. The plasticity of an IDR permits dynamic conformations that regulate cellular and biological functions.
The new study developed inhibitors that bound to the TADs of the androgen receptor, a therapeutic target for prostate cancer. While therapeutic interventions often target its folded ligand-binding domain (LBD), resistance ultimately develops due to reactivation of androgen receptor signaling.
Inhibitors stabilized the protein in the inactive state to prevent the activation of genes that drive cancer growth. In animal studies, several compounds slowed prostate cancer growth more effectively than a commonly used prostate cancer treatment. Notably, several antigen receptor TAD inhibitors displayed strong binding affinities higher than, or were comparable to the LBD-inhibitor enzalutamide, with dissociation constants in the picomolar to low-nanomolar range
“Most drug discovery is like designing a key for a very specific lock,” said Marianne Sadar, PhD, professor of pathology and laboratory medicine at the UBC faculty of medicine, distinguished scientist at BC Cancer, and co-corresponding author of the study. “But disordered proteins don’t behave like locks at all, they’re more like moving strands of spaghetti.”
“This study shows that proteins previously thought to be undruggable can be drugged with remarkable efficacy,” she continued. “The findings could have profound implications for the treatment of cancer and other diseases, providing a roadmap for the development of new treatments.”
“What surprised us was how effectively these molecules could attach to a protein that doesn’t have a fixed structure,” said Raymond Andersen, PhD, professor in UBC’s department of chemistry and co-corresponding author of the study. “We were able to shut down the androgen receptor even in situations where current prostate cancer drugs stop working.”
The researchers now aim to advance the most promising candidates toward clinical trials, with the goal of developing prostate cancer drugs for early intervention and with fewer side-effects.
“If the approach continues to prove successful, it could dramatically expand the number of proteins that scientists can target with medicines—turning what was once considered a dead end into a promising new frontier for drug discovery,” said Sadar.
Spheroids can be useful to model complex human tissues because they can re-create specific cell-to-cell and cell-to-matrix interactions. But spheroids are fragile, and common techniques for moving them manually—via suction—can easily damage them. In tissue engineering, the tiniest bit of improper force can harm a living culture. Now, a force-sensing miniature robot—a mobile microgripper (MMG)—has been developed that can handle spheroids with care.
“Other techniques for cell spheroid bioassembly can affect the tissue construct and/or apply limited manipulation forces,” said David Cappelleri, PhD, professor of mechanical engineering and assistant vice president for Research Innovation School of Mechanical Engineering at Purdue University. “The force-sensing MMG presented here addresses these current issues by allowing the safe bioassembly of different spheroids into a single construct.”
This work is published in APL Bioengineering, in a paper entitled, “Force-sensing mobile microrobotic grippers for gentle and precise bioassembly of cell spheroids.”
Integrating different types of spheroids into one culture is key for tissue engineering. But individual spheroids have to be grown in place and then moved around, introducing the chance of damage to the spheroid.
The MMG is a microscopic robot made of two arms connected by a hinge for a controlled—and gentle—gripping. Also, it is controlled by magnets, which are biocompatible with spheroids, decreasing the risk of collateral damage.
“This was a big part of the design—figuring out a way to use magnetic fields for both locomotion and for controlling the opening and closing of the gripper jaws,” Cappelleri said.
The gripping force is monitored and adjusted in real time, allowing researchers to adapt to the delicate nature of the cells. After simulating the efficacy of the MMG, in vitro testing showed that the device was able to successfully move and organize spheroids into neat patterns.
The researchers also verified that the range of gripping forces exerted by the MMG was compatible with the movement and subsequent survival of the spheroids.
Currently, the robot can successfully assemble the spheroids in a cellular “sheet,” but in the future, the researchers want to use their tiny robots to create full engineered tissues. In addition, the researchers want to take their microgrippers a step further, transitioning from manual control to automated spheroid assembly.
; and Sana Biotechnology, a developer of treatments based on engineered cells. He also launched Kaleido Biosciences, a microbiome therapeutics company that