Recommendations for Research and Clinical Implementation of Ambulatory Assessment, Mood Monitoring, Digital Phenotyping, and Remote Measurement Technology in Mood Disorders: Synthesis of Systematic Review Findings

Background: Ambulatory assessment and active and passive monitoring all offer a real-time, flexible approach to assessing mood and behavior in mood disorders. Despite their potential, concerns remain regarding the performance, usability, adherence, and potential safety of these tools. Objective: This study synthesizes the findings from 7 systematic reviews, integrating quantitative and qualitative data from randomized trials, observational studies, and user experience research to evaluate the performance, feasibility, acceptability, and clinical impact of ambulatory assessment and mood monitoring in people with depression and bipolar disorder. We assessed studies over the medium or long term (3 months or more). Methods: A summary of a series of systematic reviews was carried out by the authors—including meta-analyses (for quantitative data) and meta-syntheses (for qualitative data). Eight electronic databases were searched, and mixed methods studies were included. Studies were assessed for risk of bias. The results were checked for coherence, and recommendations were made by individuals with lived experience, methodologists, and psychiatrists. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality and strength of the evidence. Results: The 111 included studies included 19,945 participants and used 69 different ambulatory assessment protocols or mood-monitoring interventions. Key barriers to implementation were identified, including performance inconsistency, adverse effects, and user disengagement. Evidence-based recommendations are provided to guide future clinical and research applications. Conclusions: Ambulatory assessment and mood monitoring hold promise in research and clinical practice, yet their implementation requires more rigorous evaluation, greater personalization, and responsible, user-centered design. Crucially, these measures can add granularity and confirmation, but additional context is often required, and none of these measures are robust enough yet to replace current outcomes.
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AI-Powered Blood Test Detects Early Retinal Damage in Diabetes 

Scientists have developed an AI-assisted prediction tool that can identify patients with type 2 diabetes at high risk of developing diabetic retinal neurodegeneration (DRN) before symptoms appear. Their findings were published today in the journal PLOS Medicine.

“Our study suggests that early retinal nerve damage in diabetes leaves measurable signals in the blood,” write the authors of the study, led by Wei Wang, MD, PhD, associate professor at the Guangdong Provincial Clinical Research Center for Ocular Diseases. “These findings suggest that a simple blood test analyzed with artificial intelligence may help identify people with diabetes who are at highest risk of early retinal nerve damage, well before visible damage appears on the retina.”

Type 2 diabetes affects more than half a billion people worldwide, carrying with it an increased risk of long-term complications including progressive neurodegeneration. Retinal nerves are among the earliest tissues to be damaged, which can eventually lead to severe visual impairment and vision loss. However, current diagnostic methods can only detect DRN once the retina has already suffered irreversible damage. 

Wang and colleagues developed a machine learning algorithm called Pro-DRN using data from 1,218 participants in the Guangzhou Diabetic Eye Study, all of whom were diagnosed with type 2 diabetes but had not yet developed DRN at the time of enrollment. The AI model integrated proteomics data from blood samples with yearly retinal images collected over a six-year follow-up period. 

This led to the identification of 71 proteins associated with the development of DRN. Among them, the proteins most consistently driving accurate predictions were ACTA2, COL6A3, and HSPG2, which are key structural components involved in maintaining the integrity of the nerve and muscle tissue in the eyes. These results were then validated in an independent cohort of 502 patients from UK Biobank, where the core effects and protein signals were reproduced. 

Pro-DRN has been deployed as an interactive, web-based risk assessment tool that doctors can use to support early DRN screening and monitor patient evolution over time. Individuals identified as being at high risk of DRN could benefit from more frequent checkups and early interventions aimed at preventing or slowing down progressive neurodegeneration. 

Because DRN is one of the first symptoms of nerve degeneration induced by diabetes, early detection could also signal the onset of nerve injury elsewhere in the body. Such damage can contribute to cognitive impairment, dementia, and peripheral neuropathy, which can cause loss of sensation and motor control in the hands, feet, and other extremities. A single eye test could therefore provide valuable insights into the overall health of the nervous system. 

In addition, the proteins identified to be involved in DRN progression could be investigated as potential targets for the development of novel therapies. Furthermore, the AI-based tool could also prove valuable for the selection and stratification of participants in clinical trials evaluating neuroprotective strategies designed to prevent or delay nerve damage. 

“Pro-DRN may help move diabetic eye care from detecting established damage toward earlier, molecularly informed risk stratification, so that closer monitoring and future neuroprotective interventions can be directed to the people most likely to benefit,” Wang and colleagues write. 

The post AI-Powered Blood Test Detects Early Retinal Damage in Diabetes  appeared first on Inside Precision Medicine.

Disease Detection Gets Boost from Keck’s New Brain Reference Map

Investigators at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine say they have created one of the largest reference models ever developed for the human brain, using diffusion MRI scans from more than 54,000 people to chart how the brain’s communication pathways develop, mature, and decline across the lifespan.

Published in Nature Communications, the study “Lifespan normative modeling of brain microstructure” provides the equivalent of growth charts for the brain’s white matter, the vast network of neural wiring that allows brain regions to communicate, according to the Keck team, which adds that the novel tool offers researchers a new way to detect subtle patterns linked to aging, Alzheimer’s disease, schizophrenia risk, and other neurological and psychiatric conditions.

“Just as pediatric growth charts help clinicians determine whether a child’s height or weight is developing as expected, these brain charts provide a reference for how the brain’s neural pathways typically change over the lifespan,” said Julio E. Villalón-Reina, MD, PhD, a postdoctoral researcher at the Stevens INI and the study’s first author. “That gives us a powerful new way to identify when an individual’s brain wiring falls outside the expected range.”

To study white matter, the team used diffusion MRI, an imaging method that tracks how water moves through brain tissue. Because water movement is shaped by microscopic features such as nerve fibers and myelin, diffusion MRI can reveal subtle changes in tissue organization not visible on standard brain scans.

After compiling diffusion MRI data from 54,583 individuals across 19 international datasets, the researchers built statistical growth and decline charts for the brain’s neural pathways.

The researchers focused on four widely used measures of white matter microstructure across 21 major brain regions. By modeling how these measures vary by age and sex, they generated lifespan curves and percentile ranges that show what is typical at different stages of life.

Statistical charts compiled from a large population allow brain abnormalities to be detected in new individuals. [Stevens INI]
Statistical charts compiled from a large population allow brain abnormalities to be detected in new individuals. [Stevens INI]

The results revealed that white matter follows distinct developmental and aging trajectories, with some measures reaching peak maturity in early adulthood and others later in midlife.

“Brain development and brain aging are not uniform processes,” continued Villalón-Reina. “The brain’s neural pathways mature on distinct timelines, and some are more vulnerable to decline than others. Our model reveals this structure by merging data on a truly global scale.”

The scientists also discovered evidence for a longstanding theory of brain aging, sometimes described as last in, first out. According to this theory, brain pathways that develop last in childhood and adolescence tend to be more susceptible to decline in older age. The researchers observed that white matter regions that mature later did indeed decline faster in old age, offering new insight linking brain development and aging.

To demonstrate the model’s practical value, the researchers applied it to clinical datasets from people with mild cognitive impairment, dementia, and 22q11.2 deletion syndrome, a genetic condition that increases risk of schizophrenia.

In each case, the model identified alterations in the brain’s circuitry that deviated from age-expected norms. Importantly, these deviations were not identical across individuals with the same diagnosis, highlighting the value of a person-specific approach.

Paul M. Thompson, PhD, associate director of the Stevens INI and senior author of the study
Paul M. Thompson, PhD, associate director of the Stevens INI and senior author of the study

“This monumental study took seven years to complete,” explained Paul M. Thompson, PhD, associate director of the Stevens INI and senior author of the study. “The vast scale of the data and the fine scale of the brain features assessed means we can now evaluate your neural pathways relative to other people of the same age, sex, and demographics. We can see how your brain differs from what we would expect for a person of your age and sex, giving us a tool to use in clinical trials of treatments for dozens of brain diseases.”

When applied to people with dementia and mild cognitive impairment, the model detected atypical white matter patterns in brain regions involved in memory and interregional communication. In people with 22q11.2 deletion syndrome, it identified deviations in multiple key neural pathways, helping researchers discover which brain systems develop differently.

The reference charts may also help researchers evaluate treatments by tracking whether a person’s white matter measures move closer to the expected range, or whether a treatment slows the shift away from healthy patterns over time. The charts will now be used to compare more than 30 brain diseases and conditions, offering a common framework for studying how different disorders emerge, progress, and respond to intervention.

The models are also a publicly available resource that can be extended as additional brain imaging data become available. The methods are now being used to study neurological, psychiatric, and neurodevelopmental disorders by providing a common reference standard for white matter microstructure across the lifespan.

“This study demonstrates the power of large-scale, international data sharing to create tools the entire research community can use,” pointed out Arthur W. Toga, PhD, director of the Stevens INI and provost professor at USC. “By establishing a lifespan framework for the brain’s communication pathways, this work opens new opportunities to detect subtle disease-related changes, compare conditions more rigorously, and move toward a more individualized understanding of brain health.”

 

 

 

 

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Mature Intestinal Cells Revert to Stem-Like State to Sustain Colorectal Cancer

Researchers at the Stevens Institute of Technology have identified a mechanism that helps explain how colorectal cancer (CRC) develops, persists, and resists treatment. The research, published in the journal Cell Death & Disease, shows that mature intestinal cells that revert to a stem cell-like state can sustain tumor growth more effectively than mutated intestinal stem cells, a finding that could inform new drug development strategies focused on preventing CRC recurrence.

“Our study suggests that intestinal cancers can arise not just from damaged stem cells, but also from cells that revert into stem-like cancer cells,” said senior author Ansu Perekatt, PhD, an assistant professor of chemistry and chemical biology at Stevens Institute of Technology, “and they may contribute to why colorectal cancer can be diverse and resistant to treatment.”

Colorectal cancer is the second leading cause of cancer-related death worldwide. Cancer stem cells are known to play a role in tumor growth, metastasis, treatment resistance, and relapse. The new study focused on understanding how these cancer-driving stem cell populations emerge within the intestinal epithelium.

Two different models have been proposed for how colorectal cancer can develop. The most widely held belief is the “bottom-up” model which suggests that mutations in stem cells initiate tumor formation. By comparison, the “top-down” model suggests that mature epithelial cells acquire mutations, dedifferentiate into stem-like cells, and then drive tumor growth. Histological features observed in many human colorectal tumors have suggested a luminal, or top-down, origin.

Under normal conditions, Lgr5-positive stem cells reside in intestinal crypts and their role is to replenish the intestinal lining. As their progeny migrate from the crypts toward the villi in the intestine walls, they stop dividing and become specialized mature cells. However, previous research has shown that the intestinal epithelium is highly plastic and that differentiated cells can regain stem cell characteristics under certain conditions.

To better understand the biology of these pathways, the Stevens employed mouse model carrying Smad4 loss-of-function and β-catenin gain-of-function mutations, to mimic two common drivers of human colorectal cancer. They then tracked the behavior of both stem cells and differentiated epithelial cells.

The researchers also performed single-cell RNA sequencing to characterize the cellular populations that emerged during tumor initiation and progression allowing them to compare mutant stem cells residing in the crypts with dedifferentiation-derived stem-like cells arising in the villi.

The data showed that mutant Lgr5-positive stem cells in the crypts were at a competitive disadvantage. While they carried cancer-associated mutations, many were displaced and ultimately replaced by normal stem cells. At the same time, a subset of progenitor and epithelial cells underwent dedifferentiation and reacquired stem-cell properties making them capable of sustaining tumor growth.

“We don’t know why they change and why only a subset changes,” Perekatt said. “It’s very random, very sporadic. But when they change, they develop tumors.”

According to the study, dedifferentiating epithelial cells showed early expression of both CD44 and Lgr5, markers associated with stemness and tumor initiation. The Stevens team also found abnormal activation of Notch signaling in villus epithelial cells before the formation of tumor-associated crypt structures, suggesting that this pathway may contribute to the acquisition of stem-like properties.

The dedifferentiation-derived cells showed growth-factor independence, which allows them to proliferate without relying on the supportive niche environment normally required by stem cells. They also exhibited metabolic adaptations associated with tumor survival.

The study also found evidence of stem-cell heterogeneity within tumors. Single-cell analysis identified populations with distinct proliferative, signaling, and metabolic states. One mutant stem-cell cluster exhibited cancer-associated and embryonic stem cell-like gene signatures, while other clusters appeared more quiescent.

“Our findings suggest that metabolic adaptations and dedifferentiation-driven stem cell heterogeneity may enhance adaptability and confer a selective advantage driving top-down tumorigenesis,” the researchers wrote.

The findings have implications for current and future treatment strategies. Many therapies focus on eliminating actively growing cancer cells, but the study suggests that stem-like cells generated through dedifferentiation may remain capable of regenerating tumors after treatment. Targeting the mechanisms that enable mature epithelial cells to revert to a stem-like state could prove an effective method for preventing cancer recurrence.

“If you are only treating the cells that become cancerous without targeting the cells that acquired the de novo stemness, the cancer will likely come back,” Perekatt said. “So it’s really important to understand what causes this reversion to stemness, in order to develop new and effective therapies for colorectal cancers.”

Future research will focus on unanswered questions raised by the study, including the source of the Notch signals that trigger dedifferentiation, the transcriptional programs activated during this process, and the metabolic vulnerabilities of the resulting stem-like tumor cells.

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New national action plan targets gaps at the intersection of mental health and criminal justice.

FOR IMMEDIATE RELEASE

OTTAWA, ON – The Mental Health Commission of Canada (the Commission) today released “Finding New Pathways: An action plan for criminal justice and mental health in Canada”. The plan provides an evidence-based roadmap to address systemic gaps in care, coordination, and community supports, recognizing the impact of mental health on the criminal justice system.

Many are working to improve outcomes but needs remain high and progress is uneven. This action plan is a practical pan-Canadian reference point that seeks to contribute to the mental health and wellbeing of all individuals who interact with the criminal justice and forensic mental health systems, including those who work within them.

Developed through a rigorous five-year process, the action plan was shaped by input from national subject matter experts, research, and the lived and living experiences of justice-involved individuals and system workers. The action plan comes at a critical time, as individuals experiencing mental health challenges currently comprise roughly three-quarters of all federally incarcerated people in Canada.

“Meaningful and sustainable transformation is within reach for Canada,” said Lili-Anna Pereša, President and CEO of the Mental Health Commission of Canada. “While these transformative changes cannot be implemented overnight or by one group alone, this action plan serves as a starting point. It centralizes evidence-based approaches designed to break the cycle of recidivism and prioritize prevention, diversion, end-to-end supports and continuity of care.” The action plan stands on three strategic pillars:

  • Care, not criminalization: Ensuring all people in Canada have access to supports that help prevent involvement with the criminal justice system, and prioritizing diversion for those with mental illnesses.
  • Care during criminal justice involvement: Providing access to high-quality, trauma-informed, and culturally safe health and social supports for those within the system.
  • Care after criminal justice involvement: continuity of care and seamless integration into community-based mental health
    and substance use services upon release.

“Finding New Pathways” identifies 68 specific recommendations across individual, community, institutional, systemic, and societal levels. It pays particular attention to priority populations, including people from First Nations, Inuit, and Métis, and African, Caribbean, and Black, and other equity-deserving groups who are currently overrepresented in the justice system and face distinct mental health needs.

The action plan further highlights the critical importance of supporting the psychological health and safety of workers within the criminal justice and forensic mental health systems, noting that public safety personnel are significantly more likely to experience symptoms consistent with mental disorders than the general population.

Howard Sapers, current executive director of the Canadian Civil Liberties Association, former Correctional Investigator of Canada, and project advisor for the action plan, emphasized the necessity of these reforms: “ or too long, Canada’s criminal justice system has been asked to shoulder responsibilities it was never designed to carry. The over representation of people with mental health needs in police encounters, courts, and correctional facilities is a predictable consequence of systemic gaps in care, coordination, and community supports. The Mental Health Commission of Canada’s National Action Plan offers something we have been missing for years: a coherent, evidence-based roadmap that prioritizes health, human rights, and dignity.”.

Media Contact:

For English requests, please contact Josie Sabatino at jsabatino@summa.ca; 250-649-6856.

For French requests, please contact Carlene Variyan, cvariyan@summa.ca; 613-601-7456.

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STAT+: Radiopharmaceutical shows promise in post-Pluvicto setting

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Good morning. Today, we’re looking at mixed reactions to a closely watched immunology trial and growing scrutiny of a type of telehealth business model.

The need-to-know this morning

  • Vera Therapeutics and the FDA reached an agreement to allow Vera to accelerate the analysis of a confirmatory Phase 3 study involving atacicept, its treatment for the chronic kidney disease IgA nephropathy. The drug is already under review for accelerated approval, with a decision expected by July 7. The new FDA agreement will allow Vera to analyze its Phase 3 study, needed for full approval, in the third quarter, rather than wait for an additional year of data to accrue.

Abivax’s positive data weighed down by cancer concerns

Abivax said yesterday that its experimental treatment for ulcerative colitis showed significant efficacy in a closely watched maintenance trial.

Continue to STAT+ to read the full story…

Kinase Droplets Activate Growth Signals, Path for Cancer Therapy

A new study published in Cell Reports titled, “Kinase condensates enrich ATP and trigger autophosphorylation,” suggests that cellular phase separation, a mechanism that organizes biomolecules into dense, liquid-like condensates, may play a previously underappreciated role in regulating kinase activity. The findings suggest that aberrant condensate formation could contribute to oncogenic signaling while also offering new opportunities for drug targeting. 

“Many biological molecules have this propensity to spontaneously separate,” said Lindsay Case, PhD, assistant professor of biology at Massachusetts Institute of Technology (MIT) and corresponding author of the study. “We were really interested in asking, if we have these kinases forming droplets, what is the consequence of that in the context of signaling?” 

Phase separation occurs when proteins condense into highly concentrated liquid-like droplets within cells, analogous to oil droplets separating from vinegar. Although biomolecular condensates have emerged as important organizers of cellular processes, their impact on kinase signaling has remained incompletely understood. 

The researchers examined three kinases: focal adhesion kinase (FAK), Mst2, and Abl. Across all three systems, condensate formation increased kinase activity by concentrating enzymes and substrates, thereby promoting phosphorylation reactions. 

For FAK, the team found that elevated protein levels were sufficient to drive droplet formation and activate downstream growth signaling. The findings raise the possibility that FAK overexpression in tumors could promote constitutive signaling through condensate formation, potentially contributing to cancer progression and metastasis. 

“It was surprising that just by condensing this protein into a droplet, you can actually turn on a signaling pathway that should be turned off,” said Case. “If FAK concentration is too high, you’re always getting these droplets and you’re always signaling, regardless of what the receptors that are supposed to be controlling this are doing.” 

Mst2 and Abl also phase separated at high concentrations, which led to increased activity. For Mst2, phase separation is a strategy that healthy cells use to control the Hippo signaling pathway, which promotes cell growth and survival. Phase separation can also lead both enzymes to phosphorylate additional targets, and activate different signaling pathways. 

“It’s not just that you’re getting faster phosphorylation, but in those cases, the patterns of what is actually getting phosphorylated were very different inside of the droplet compared to what might be happening in a non-droplet context,” Case says. “The kinase is able to phosphorylate amino acid residues beyond the set of canonical sites that have been described before.” 

Mechanistically, the team found that kinase condensates selectively concentrate ATP, the phosphate donor required for kinase activity. Positively charged regions within kinases appear to recruit negatively charged ATP molecules to support phosphorylation. 

Using machine-learning analysis, the investigators predicted that approximately 45% of the roughly 500 human kinases possess the molecular features needed to form similar condensates. The findings suggest that phase separation may represent a widespread regulatory mechanism that could influence both normal cellular signaling and disease-associated kinase activity. 

In future work, Case hopes to explore designing drugs that could mimic ATP’s ability to be attracted into droplets within a cell, which could reduce side effects.

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Circio and GenAssist Collaborate on Gene Therapy for Muscle Disease and In Vivo Cell Therapy

Oslo, Norway-based Circio and Suzhou, China-based GenAssist entered into a research collaboration to develop circVec-enhanced AAV vectors specifically engineered for in vivo cell therapy and targeted, low dose systemic gene therapy.

Genetic muscle disease is an area of major unmet medical need, where current gene therapy’s high dosing requirements are associated with severe toxicity. By integrating Circio’s and GenAssist’s complementary technologies, the parties aim to develop joint next generation of AAV gene therapy candidates, according to a Circio spokesperson. The focus is on addressing genetic muscle conditions where high and broad muscle-specific expression is required at substantially lower therapeutic AAV doses than can be achieved by conventional AAV gene therapy.

“Our second-generation AAV platform establishes a new benchmark for safety, utilizing highly tissue-specific, de-targeted capsids to dramatically lower systemic dosing while eliminating off-target toxicity,” said Chunyan He, PhD, CEO of GenAssist. “Through our collaboration with Circio, we integrate their unique circular RNA technology. This partnership directly addresses the core demands of next-generation genetic medicine, overcoming the traditional dose-expression trade-off to deliver safer and more effective therapies.”

In addition, Circio and GenAssist will explore the potential of generating joint in vivo CAR T candidates for oncology and autoimmune applications. The collaboration will involve production of novel AAVs combining GenAssist´s T-cell targeting with the circVec expression cassette from Circio. The combined AAVs will subsequently be tested in vitro and in vivo, and if successful, candidates for further development will be nominated for preclinical development.

“The targeted AAVs developed by GenAssist have the ability to specifically and efficiently transduce muscle or T-cells upon systemic delivery with near-complete liver de-targeting,” added Thomas Hansen, PhD, CTO of Circio. “The partnership between Circio and GenAssist will aim to evaluate whether the enhanced circVec expression acts synergistically with these targeted capsids and promoters.

“This fits perfectly into Circio’s strategy of testing circVec in multiple tissues using different AAV variants, both internally and externally. This will allow us to identify new therapeutic avenues where circVec delivers a benefit, and forge partnerships potentially enabling multiple future development opportunities. China is a particularly interesting geography, with cutting edge science and accelerated pathways to establish early clinical data.”

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Detection of Self-Harm in Electronic Mental Health Records Using Privacy-Preserving Local Language Models: Methodological Study

Background: Self-harm is the strongest risk factor for suicide and an important outcome for mental health care. Although prevalent in clinical populations, it is often imprecisely captured in routinely collected clinical data, where it is often recorded and stored as unstructured free text. Contemporary language models, such as GPT (OpenAI) and Gemini (Google), can analyze free-text clinical notes, but such models may violate data governance of processing sensitive patient data. Objective: This study aimed to evaluate whether a privacy-preserving language model running entirely within an institution’s secure computing infrastructure (here, the UK National Health Service [NHS]) could accurately identify the presence and timing of self-harm using electronic health records from secondary mental health care. Methods: Clinical notes were drawn from Oxford Health NHS Foundation Trust using a multistage workflow: (1) a random sample of 1000 patients with a psychiatric diagnosis, defined according to the (; codes F00–F99); (2) candidate-note identification using a Gemma3-4b language model to flag notes containing self-harm content; and (3) from those candidates, 1352 randomly sampled notes were selected for expert annotation, resulting in gold-standard corpus enriched for self-harm content. Clinical notes were annotated for the presence of self-harm and its timing (≤90 days, >90 days, or unknown). A privacy-preserving locally served 27-billion-parameter Gemma 3 language model (“Gemma3-27b”) was used as the core model. Prompts were systematically developed and refined using a labeled development set to identify self-harm and generate a structured output per clinical record. Gemma3-27b performance was compared against a strong baseline multilabel text classification model based on robustly optimized BERT pretraining approach (RoBERTa), a transformer-based language model architecture. Model performance was evaluated using precision, recall, and the -score (harmonic mean of precision and recall), with 95% CIs estimated from 1000 bootstrap samples with replacement. Results: Gemma3-27b outperformed the RoBERTa classifier across all categories, achieving Precision=0.92, Recall=0.92 (sensitivity), and -score=0.92 for notes containing self-harm, and Precision=0.97, Recall=0.97 (specificity), and -score=0.97 for notes without self-harm. For the 51 notes labeled as recent self-harm in the held-out test set, Gemma3-27b achieved Precision=0.84, Recall=0.75, and -score=0.79. The global weighted -score of Gemma3-27b across all categories was 0.88, compared to 0.85 for RoBERTa. Conclusions: With systematic prompt development on a labeled development set, but no gradient-based fine-tuning, the current Gemma3-27b language model matched or exceeded a fine-tuned RoBERTa classifier for ascertaining self-harm events and their timing. Aggregate gains were modest, while improvements were largest in the most challenging, lower-frequency timing categories. On a simplified binary recent-versus-other task, RoBERTa performed marginally better, indicating that supervised classifiers remain highly effective when the task is simplified and sufficient labeled data exist. This work demonstrates the technical feasibility of privacy-preserving self-harm detection within a secure NHS research environment.

Low-Cost, Portable Biotech Tools Improve Access to Bioresearch and Diagnostics

A global research team headed by scientists at University of Toronto’s Leslie Dan Faculty of Pharmacy has demonstrated the effectiveness of a suite of low-cost, portable biotechnology tools that are designed to improve access to laboratory research and diagnostics in resource-limited settings.

The newly reported study highlights how decentralized biomanufacturing tools and freeze-dried reagents can help researchers produce high-value biological materials locally—reducing reliance on fragile international supply chains and expanding access to life sciences innovation globally.

“For labs in low- and middle-income countries [LMICs], access to high-quality supplies and equipment is a chronic problem,” says research lead Keith Pardee, PhD, associate professor at the Leslie Dan Faculty of Pharmacy Pardee. “Shipping can take a long time, it’s expensive, and products often require a cold chain to retain their effectiveness. This research is in response to those challenges to develop tools that are more accessible for labs in lower-resource settings and improve research equity.”

Pardee, alongside collaborators including Camila González, PhD, at the Universidad de los Andes, Bogotá, Fernán Federici, PhD, at Millennium Institute for Integrative Biology (iBio), Santiago, and Lindomar Pena, PhD, at Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife, reported on the study in Science Advances. In their paper, “International multisite implementation of distributed cell-free protein biomanufacturing to advance health and research equity,” the authors concluded, “This study lays the foundation for fundamental shifts in biotechnology manufacturing practices in LMICs and developing nations, moving from reliance on centralized and outsourced production facilities to adopting decentralized, local production platforms.”

“Emerging biotechnologies hold transformative potential to strengthen economic and health security, while benefiting the planet,” the authors wrote. However, they pointed out, “Access to advanced tools, such as molecular diagnostics, life-saving treatments, and biomanufacturing infrastructure, remains largely concentrated in wealthier regions, thereby restricting access to transformative solutions for communities that need them most.”

A key factor is the reliance on centralized bioproduction systems, “… which require sophisticated, capital-intensive infrastructure and cold supply chains that are often unavailable in resource-limited settings.” Access to healthcare is similarly affected by the availability of biomanufacturing capacity and biologistics, which can slow delivery of diagnostics, delay disease control programs, and limit the ability to carry out life sciences research.

For their newly reported work the team focused on synthetic biology and cell-free systems—technologies that isolate and freeze-dry the molecular machinery needed to produce proteins commonly used in life sciences research. Because the reagents are freeze-dried, they can be shipped and stored without refrigeration, then reactivated simply by adding water. “One promising avenue to improving access is cell-free protein synthesis (CFPS), which offers the potential to empower communities through affordable, low-burden, on-site production of critical bioreagents, diagnostic tools, and therapeutic agents,” the researchers stated.

They paired these systems with low-cost, adaptable hardware, including a 3D-printed hand-powered centrifuge developed by postdoctoral fellow Mohammad Simchi, PhD, at the Leslie Dan Faculty of Pharmacy. Together, the technologies enabled teams to produce a range of research proteins and diagnostic tools in diverse settings, from conventional laboratories to remote field locations.

“With efficient, low-cost systems in place, rapid on-site production of high-value bioproducts for research, including growth factors, vaccines, and diagnostic enzymes, became achievable within a single day and at a fraction of the typical cost,” they commented.

Using the platform, researchers successfully produced growth factors used in life sciences research and therapeutics, as well as a SARS-CoV-2 vaccine candidate tested in mice and diagnostic tools targeting several clinically relevant pathogens. Using molecular, cell-based, animal model, and clinical sample testing, the bioproducts were validated through proof-of-concept studies and multisite clinical trials. “Direct comparisons with high-cost commercial reagents, the current gold standards, demonstrated similar performance, efficiency, precision, and reproducibility,” the investigators further noted.

First author Severino Jefferson Ribeiro da Silva, PhD, a postdoctoral fellow in Pardee’s lab, said, “Our work shows that it is possible to produce high-value bioreagents on site, essentially anywhere. Through this work, we demonstrated our tools across diverse international settings while maintaining performance comparable to commercial products.”

The authors say that, to their knowledge, the study is the first to translate cell-free biomanufacturing from laboratory to real-world use, across multiple geographic settings, including those that historically have had limited access to the bioeconomy. “By prioritizing accessibility, affordability, and reproducibility, we show that cell-free biomanufacturing is a transformative tool for expanding global research capacity and, ultimately, health equity and participation in the bioeconomy.”

A key component of the project involved testing the systems in a variety of environments across Canada and internationally. Da Silva travelled to the Algonquin Highlands to evaluate diagnostic tools for tick-borne pathogens and tuberculosis, while graduate student Quinn Matthews travelled to the Yukon where he produced and purified proteins using the portable system on a mountain outside Whitehorse.

Collaborators in Chile, Brazil, Colombia, and India also tested the systems, helping ensure the technologies addressed the practical realities faced by researchers in different regions. The project involved extensive international collaboration, including regular meetings, student exchanges and knowledge sharing among participating teams.

Da Silva says the research team experienced first-hand many of the logistical challenges their collaborators routinely face, including lengthy customs delays and damaged shipments containing critical reagents.

“Those experiences highlighted how dependent many researchers and labs still are on fragile international supply chains. If a shipment is delayed, an entire project can stop,” says da Silva. “This work makes it possible to reduce that dependency by enabling local production of key proteins directly at the point of need.”

The researchers say the long-term goal is to help research labs in remote and underserved regions gain access to high-quality diagnostics, research reagents and biomanufacturing capabilities produced closer to home, strengthening resilience against future supply chain disruptions while empowering their research capacity and address local healthcare needs. “With their low cost and operational simplicity, we see these platforms and similar disruptive technologies … as part of a new generation of tools that will help shape a future in which bioreagents, advanced diagnostics, and life-saving therapeutics are accessible to all.”

Da Silva added, “This work is really about access and scientific empowerment. Many labs worldwide have the expertise and ideas to conduct life sciences and applied science research, but they face major challenges accessing key bioreagents and essential materials. Decentralized biomanufacturing could help reduce those barriers and make research and diagnostics more accessible globally.”

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