Background: People who are incarcerated face significantly higher health risks than the general population, yet deaths in custody remain underreported and poorly monitored by public health systems. Although the federal Death in Custody Reporting Act requires reporting of all deaths in correctional facilities to the US Department of Justice, reporting has been inconsistent, delayed, and often publicly inaccessible. Consequently, researchers have turned to press releases issued by correctional agencies as one of the few timely sources of information on deaths in custody. However, these press releases vary widely in content and structure, making standardized data extraction difficult. Crowdsourcing platforms such as Amazon Mechanical Turk (MTurk) may offer a faster, low-cost method for gathering data, but their utility in this setting remains untested. Objective: This pilot study evaluated whether MTurk could be used to extract structured information from press releases about deaths in custody. Methods: We selected 144 press releases describing deaths between 2000 and 2023 from state prison systems and Immigration and Customs Enforcement. Each press release was assigned to 3 MTurk crowd workers (who were required to be English speaking and located in the United States), resulting in 432 individual responses. Workers were informed in advance that the task involved reviewing sensitive content related to deaths in custody. Crowd workers completed a 16-question form aligned with Death in Custody Reporting Act variables, including age, race and ethnicity, date of death, and facility location. Data quality was assessed using strict concordance (all 3 responses matched), 2-way concordance (2 of 3 responses matched), and qualitative review of common errors. Task completion time was also recorded. Sampling included complete subsets of selected press releases and a stratified subset from systems with more complex reporting formats. Results: All 144 entries were completed within 48 hours. However, agreement across crowd workers was low: strict concordance was 14.2% (20/144) for age, 12.3% (18/144) for race or ethnicity, and 11.4% (16/144) for date of birth. Qualitative review identified frequent errors, missing data, and inattentive or automated responses. Crowd workers often misinterpreted system-specific terminology or copied placeholders instead of extracting information from the source. The low agreement indicated that this baseline MTurk configuration produced insufficient data quality for more resource-intensive use. Conclusions: MTurk enabled rapid task completion but produced low-quality results when applied to extracting structured data from carceral press releases. These findings suggest that general crowdsourcing platforms are poorly suited to complex data abstraction tasks without additional training or oversight. With improved task design or support from artificial intelligence tools, crowdsourcing may help address gaps in the surveillance of deaths in custody. Long-term improvements will require consistent, transparent, and standardized reporting practices across correctional institutions.
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Factors Influencing the Initiation and Continued Engagement of Digital Mental Health Tools Among Adults: Theory of Planned Behavior–Informed Systematic Review
Background: Digital mental health tools (DMHTs) offer scalable support, but engagement varies. Understanding the shapes of initiation and ongoing use is essential for effective design and implementation. Objective: This study aims to synthesize determinants of adults’ initiation and engagement with DMHTs, organized through two lenses: (1) psychological factors aligned with the theory of planned behavior (TPB) and (2) design and access features. Methods: A systematic search of 9 databases (June 2025) identified qualitative and mixed methods primary studies reporting end-users’ experiences with DMHTs. Studies were screened and reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal used quality assessment with diverse studies (QuADS). Data were synthesized using a framework-guided thematic approach, mapping findings to TPB constructs and complementary design and access domains. Results: A total of 22 studies met inclusion criteria. Findings clustered into 2 interdependent domains. TPB constructs explained how beliefs, social expectations, and perceived control shaped decisions to start and persist with DMHTs. Design and access features frequently acted through these same pathways, especially by altering perceived behavioral control (PBC), with cost, connectivity, device constraints, and time flexibility affecting feasibility, with content design and privacy shaping perceived value and trust. Perceived fit (goals, cultural or linguistic relevance, and routine alignment) consistently influenced both initiation and continuation. Several features operated bidirectionally; depending on context, the same feature could facilitate or hinder engagement. Conclusions: Engagement with DMHTs is jointly determined by users’ beliefs and the design and access conditions within which tools are offered. Implementation should pursue a dual strategy, strengthening willingness to seek support (addressing attitudes, norms, and perceived control) while engineering low-effort, trustworthy, and context-appropriate experiences. Priorities include equity-focused policies (data costs, devices, and connectivity), transparent data practices, co-design with diverse communities, and consistent, theory-informed outcome measures.
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Reducing Intrusive Trauma Memories Using a Brief Mental Imagery Competing Task Intervention: Case Series of Trauma-Exposed Women in Iceland
Background: There is a need for scalable and simple interventions for trauma-exposed people. In this case series, we built on our previous case study and case series findings and further explored the use and potential effectiveness of a brief novel intervention to reduce the number of past intrusive memories of trauma. The imagery competing task intervention consists of a memory reminder and the visuospatial task Tetris played with mental rotation, targeting 1 intrusive memory at a time. Here, we test remote delivery of the intervention, including guidance from researchers without specialist mental health training, in a sample of women in Iceland with current intrusive memories from trauma. Objective: In a case series of trauma-exposed women, we aimed to explore whether this brief novel intervention reduces the number of established intrusive memories (primary outcome) and improves general functioning and symptom reduction in posttraumatic stress, depression, and anxiety (secondary outcomes). The acceptability of the intervention along with adaptations, that is, delivery by psychology students without specialist mental health training and digital delivery, was explored. Methods: Participants (N=8) monitored the number of intrusive memories from an index trauma (occurring 3‐16 years previously) in a daily diary at baseline, during the intervention, and postintervention at 1-month and 3-month follow-ups. The intervention was delivered digitally with guidance from clinical psychologists or psychology students. A repeated AB design was used (“A”: preintervention baseline, “B”: intervention phase). Intrusions were targeted one by one, creating repetitions of an AB design (ie, length of baseline “A” and intervention “B” varied for each memory). Results: The number of intrusive memories reduced for all participants from the baseline phase compared with the intervention phase, although the reduction was minimal for 2 participants (6.3%‐93%). The number of intrusive memories continued to reduce for 6 out of 8 participants (58%‐100% reduction at 1-month follow-up; 72%‐100% reduction at 3-month follow-up). Symptoms of posttraumatic stress, depression, and anxiety were reduced for most participants postintervention and continued to decrease during the follow-up periods. Functioning was improved for 7 of the 8 participants from baseline to postintervention and continued to improve at the follow-up assessments for 3 participants. The intervention delivered digitally and partly by students was perceived to be an acceptable way to reduce the frequency of intrusive memories by all participants (mean rating 9.5 out of 10). Conclusions: Data from this case series of traumatized women provide preliminary evidence for the effectiveness of this novel brief intervention in reducing intrusive memories of trauma occurring several years ago and in improving functioning and reducing core symptom burden. This study will inform a randomized controlled trial of this novel intervention, which may have considerable implications for large-scale clinical management of traumatized populations. Trial Registration: ClinicalTrials.gov NCT04209283; https://clinicaltrials.gov/study/NCT04209283 International Registered Report Identifier (IRRID): RR2-10.2196/29873
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Exchange Marketplace Launched to Help Stalled Cell and Gene Therapies
A type of exchange marketplace for cell and gene therapies has launched to try and reinvigorate and relaunch candidate therapies that are no longer being developed due to financial constraints, despite having good science behind them.
CGTxchange, an online platform enhanced by artificial intelligence, is the brainchild of the American Society of Gene and Cell Therapy (ASGCT) and the Orphan Therapeutics Accelerator. The latter was set up in 2024 as a patient‑centered, non‑profit biotech accelerator that acquires “shelved” clinical‑stage therapies for ultra‑rare diseases and completes their development and commercialization so patients can actually access them.
The new platform was launched at the ASGCT conference in Boston and is designed to help stalled assets to find a new home. This is designed to address funding pull‑backs, program terminations, and company exits, which are forcing hundreds of cell and gene therapy programs to be discontinued or indefinitely paused despite having good scientific promise.
CGTxchange will link up companies who want to develop their assets with funders and partners who are looking for new development opportunities in cell and gene therapy.
“The cell and gene therapy field has built an extraordinary base of clinical evidence, and yet too many of those programs sit on the shelf for reasons that have nothing to do with the science,” said Terry Flotte, MD, dean of University of Massachusetts Chan Medical School and president of the ASGCT, in a press statement.
“CGTxchange gives our community a structured way to bring those programs back into view, and to connect them with the partners and funders who can help reactivate them.”
The platform is built so that people who own assets they want to develop can securely upload information about them into a database that is then searchable by possible interested parties such as investors, nonprofits, biotechs, and academic groups. They will have to pay a fee for this service, but the press statement says, “up to 10 of the initial listings will be eligible for discounted onboarding.”
When a match is achieved then the asset owner and the interested party will come to some sort of agreement on further financing. This could include traditional or alternative development and financing models, including nonprofit and hybrid structures.
The platform can theoretically be used by people from around the world, but users must apply and be approved rather than simply signing up. According to the platform’s terms and conditions on its website, “access is restricted to authorized representatives of biotechnology companies, academic institutions, nonprofits, and accredited investors.”
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RAGE Implicated in Worsening Breast Cancer Mortality with Age
Researchers at Georgetown’s Lombardi Comprehensive Cancer Center have identified a mechanism that may help to explain why older people experience worse outcomes from breast cancer. The study in different mouse breast cancer models and in human breast cancers implicates RAGE (receptor for advanced glycation end-products), a cell surface receptor that amplifies inflammatory signaling, and which also becomes increasingly active with metastatic progression. The study findings in addition suggested that inhibiting RAGE may offer a well-tolerated adjunctive breast cancer therapy in older patients.
“Our study addresses a major gap by showing that aging dramatically increases breast cancer metastasis and that this effect depends on RAGE, a receptor on the surface of cells that fuels inflammation,” said Barry Hudson, PhD, associate professor of oncology at Georgetown Lombardi. “Most laboratory studies rely on young mice, which has limited our understanding of how aging itself alters the host environment, including immune function and chronic inflammatory states that, in turn, influence cancer behavior.” Hudson is corresponding author of the researchers’ Communications Biology published paper titled “Aging promotes a RAGE-dependent increase in breast cancer metastasis.” In their paper the authors concluded that their findings “… identify RAGE as a mechanistic link between aging and metastasis and a potential therapeutic target in older patients.” They say the findings will also be featured in the Nature portfolio special collection, Cancer and Aging.
Age is the primary risk factor for the development of adult cancers, including breast cancer, with almost half of new breast cancer diagnoses and more than half of breast cancer-specific deaths occurring in women aged 65 years and older, the authors wrote. And while advances in screening and therapy have improved survival, older women continue to have higher breast cancer-specific mortality. “Despite accumulating evidence that metastasis in murine breast cancer models increases with advancing host age, the mechanisms underlying this have not been elucidated, highlighting the need for further mechanistic studies,” the team continued.
And while breast cancer is more prevalent in older women, most cancer research in mouse models has used young, 2–3-month-old adult mice, which are about equivalent in age to 15–20-year-old humans. Timing and chance presented Hudson and colleagues with opportunities to carry out their newly reported study. During COVID, when there was reduced laboratory activity, some of the research team’s mouse colonies aged longer than originally planned. This created a rare opening to study cancer in these older animals—normally a difficult and expensive endeavor—giving the scientists the ability to directly compare how tumors behave in younger versus older mice.
RAGE is a proinflammatory molecule that is being considered as a therapeutic target in multiple aging-related diseases, including various cancers, cardiovascular and neurodegenerative diseases.
Using three different mouse models of triple-negative breast cancer (TNBC), the researchers discovered that aged mice developed substantially more lung metastases than younger mice, despite similar primary tumor growth. The team then showed that genetic deletion of RAGE in mice almost completely eliminated this age-related surge in metastasis.
Through their studies, the team demonstrated that aging increased levels of inflammatory molecules that activate RAGE. These included the proteins S100 and HMGB1, found in both primary tumors and at metastatic sites. These changes made it easier for cancer cells to invade and spread. “These findings show that aging doesn’t just increase cancer risk—it actively changes the body in ways that help tumors spread,” said Hudson. “RAGE appears to be a key mediator of these harmful age-related pathways.” In their paper the authors stated that their data “… suggest that aging promotes multiple prometastatic processes within the tumor and its microenvironment, and that RAGE is required for the induction of these inflammatory and tumor-promoting pathways in aged hosts.“
The team also analyzed breast cancer data from more than 1,000 patients and found that higher expression of AGER (the gene encoding RAGE) and related inflammatory gene signatures were associated with worse outcomes in patients, supporting the clinical relevance of their findings. They noted, “… in human breast cancers, high AGER expression, as well as enrichment for mouse tumor-derived aging- and RAGE-associated gene signatures, predicted poorer outcomes, particularly in older women …Together, these data indicate that in older individuals with breast cancer, intratumor RAGE overexpression amplifies aging-associated transcriptional programs, linking age-dependent inflammation to promote metastatic progression.”
RAGE is already being explored as a therapeutic target in several age-related diseases, highlighting its potential relevance in cancer. In prior work, the researchers had shown that the RAGE inhibitor TTP488 (azeliragon) can suppress breast cancer metastasis in preclinical models. In the current study, they also tested the drug in the lab and found that TTP488 was able to reduce tumor cell invasiveness that was induced by blood sera from aged mice.” Pharmacologic inhibition of RAGE by TTP488 (PF-04494700 or azeliragon) suppressed migration and invasion towards aged serum, further supporting the requirement of RAGE signaling for age-dependent metastasis,” the team noted.
A clinical study is underway at Lombardi evaluating TTP488 in breast cancer patients receiving chemotherapy, with a focus on safety and cognitive outcome. The drug has demonstrated a favorable safety profile in people, making it an optimal choice for further study. “TTP488 has demonstrated an excellent safety profile in Phase I/II clinical studies in older adults with Alzheimer’s disease, supporting its potential for repurposing,” the authors wrote. “Therapeutic RAGE inhibition may provide a well-tolerated means to counteract inflammaging and improve cancer outcomes in the elderly, who often face limited treatment options due to toxicity,” the investigators wrote.
“This study highlights the importance of the host environment in cancer,” Hudson added. “While cancer is often viewed as driven primarily by mutations intrinsic to tumor cells, systemic factors such as aging and inflammation play a critical role in shaping how cancers behave,” said Hudson. “Most deaths due to cancer occur because tumors spread to other organs, so understanding these influences may help identify new strategies to limit metastasis.”
The post RAGE Implicated in Worsening Breast Cancer Mortality with Age appeared first on GEN – Genetic Engineering and Biotechnology News.
Multiomic ALS Study Links Peripheral Immune Infiltration to CNS Inflammation
A new study from scientists at Northwestern University Feinberg School of Medicine sheds light on how amyotrophic lateral sclerosis (ALS) unfolds in the body. Specifically, they found that the disease proceeds through a “domino-like” sequence of events that begins with an early breakdown inside motor neurons that is followed by a damaging inflammatory response. Insights from this study could help explain why the disease worsens over time, why some patients progress faster than others, and how future treatments could be more personalized. Details of the work are available in a new Nature Neuroscience paper titled “Integrated single-cell and spatial transcriptomic profiling in ALS uncovers peripheral-to-central immune infiltration and reprogramming.”
On average, patients with ALS live three years after symptoms begin, although some can survive closer to 10 years. Exactly what drives these differences in survival is unclear. “This study reveals that ALS is not a single event but a domino-like cascade that begins inside motor neurons with TDP-43 pathology and is then amplified by a damaging immune response in the bloodstream and spinal cord,” said David Gate, PhD, director of the Abrams Research Center on Neurogenomics at Feinberg and co-corresponding author on the study.
Specifically, the study found that immune cells converge at sites of motor neuron loss and TDP-43 pathology with distinct inflammatory patterns depending on the type of ALS and how quickly the disease progresses. As Evangelos Kiskinis, PhD, an associate professor of neurology and neuroscience at Feinberg and a co-corresponding author on the study, explained it, “the intensity of spinal cord inflammation” determines “how fast the disease progresses and how long they survive.”
To gain these insights, the scientists analyzed blood and spinal cord samples from living and deceased patients with both genetic and non-genetic forms of ALS, as well as controls. As part of the study, they used single-cell RNA sequencing technology to analyze blood from 40 living ALS patients and used spatial transcriptomics to analyze spinal cord tissue from 18 deceased participants. They also compared patients with non-genetic ALS to those with the genetic form of the disease to assess how immune activity differs across ALS types and disease stages. Lastly, they examined RNA from postmortem samples of 237 ALS patients to better understand the inflammatory responses within the central nervous system.
Using these methods, “we found the immune cells we detected in the blood of people living with ALS were inflamed, and we found the genes that mediate their inflammatory response in the spinal cord at the site of motor neurons,” Gate said. “These inflamed immune cells were associated with ALS pathology, giving some credence to our theory that the immune system is detrimental. It’s responding to pathology, and it’s causing the disease to be worse.”
Additionally, patients whose disease advanced quickly had more activity in certain immune genes, while those with the genetic form of the disease had a different set of altered immune genes. In the spinal cord, these activated immune cells gathered directly at the locations of motor neuron loss and near the toxic protein buildups associated with ALS. “We saw that people with worse clinical ALS had more expression of complement genes, which are proteins that become activated as the body’s first-line immune defense against a pathogen or damage to the body,” Gate said.
Now that they have identified a direct link between the immune system and ALS, Gate and his lab plan to study samples from a wider pool of patients. “Our next step is to map exactly how this immune reaction spreads throughout the entire motor circuit: from the brain, down through the spinal cord and out to the muscles,” he said. “By profiling the motor circuit in depth, we’ll get a much clearer picture of where and when inflammation drives faster progression.”
Meanwhile, Kiskinis and his team will test for a causal relationship between TDP-43 dysfunction and inflammation. “We’re trying to really define what is the mechanism that links TDP-43 dysfunction in nerve cells with inflammatory reactions,” he said.
The post Multiomic ALS Study Links Peripheral Immune Infiltration to CNS Inflammation appeared first on GEN – Genetic Engineering and Biotechnology News.
PPG-Derived Digital Biomarker Developed for Peripheral Artery Disease Detection
A research team at the University of California, San Diego has developed a machine learning-based screening approach for peripheral artery disease (PAD) that uses a light-based technology called photoplethysmography (PPG) that can measure changes in blood volume in tissue. The researchers reported that short-duration PPG recordings in a patient’s toe, analyzed by machine learning models, identified PAD with a high degree of accuracy and may provide the basis for a scalable digital screening tool that could eventually be deployed through smartphones, pulse oximeters, and wearable devices. The team’s findings are published in npj Digital Medicine.
“PPG works by shining a light into tissue, in our case, the toe,” said co-first author Ava J. Fascetti, a PhD student in the digital health technology lab of senior author Edward J. Wang, PhD. “A photosensor measures how much light is reflected back, allowing us to detect tiny changes in blood volume: what we call the PPG signal.”
PAD is caused by plaque buildup in arteries that restricts blood flow, particularly to the legs and lower extremities. The disease affects an estimated 12 million Americans and 200 million adults worldwide. PAD substantially increases the risk of limb loss and major cardiovascular events, yet many patients are not diagnosed until later stages of disease progression. The researchers noted that the condition disproportionately affects underserved populations and is underdiagnosed in part because the current standard diagnostic, ankle-brachial index (ABI), requires specialized equipment, staff, and clinic visits.
“There exists a glaring unmet clinical need to develop technology to meet the demands of modern practice,” the researchers wrote. Further, ABI testing, introduced about 60 years ago, has has remained largely unchanged and has long-standing barriers to widespread use in primary care and under-resourced settings.
The current study originated from discussions between co-first author Mattheus Ramsis, MD, and assistant professor of medicine and medical director of cardiology informatics, and co-author Elsie G. Ross, MD, an associate professor of surgery in vascular and endovascular surgery, who noted that vascular labs conducting ABI testing often also collected toe PPG waveforms.
“The light-bulb went off for me at that moment,” Ramsis said.
PPG works by shining light into tissue and measuring backscattered light associated with blood volume changes. PPG has previously been used to identify cardiovascular and metabolic conditions including diabetes and atrial fibrillation. Earlier research efforts to use PPG for PAD detection had relied on small datasets, long recordings and less interpretable deep-learning approaches.
For their approach, the UCSD team assembled a dataset containing more than 10,000 toe PPG recordings from more than 3,500 patients who underwent ABI testing at UC San Diego Health between 2020 and 2025. Using these data, the researchers extracted 78 waveform features from the PPG signals that correlated significantly with ABI measurements. Those features were then used to train an explainable support vector machine model designed to identify PAD from PPG data alone.
Ramsis said the model correctly distinguished PAD cases approximately 83% of the time using only PPG data, compared with roughly 60% to 65% performance typically achieved using clinical risk-factor assessments alone. Incorporating smoking status of the patients further improved the performance of the new method.
Importantly, the model performed consistently across Black, Hispanic, and White patient populations, and among patients with diabetes, coronary artery disease, and end-stage renal disease. The researchers also reported similar performance across two UC San Diego Health campuses that used different equipment and staff.
The investigators noted that the physiologic basis for their findings align with established vascular biology. In PAD, reduced blood flow and arterial stiffness alter the morphology of PPG waveforms. Healthier patients demonstrated steeper systolic upstrokes and narrower waveform widths, while patients with PAD showed more dampened signals.
“Our findings support the existence of a reproducible PPG-derived digital biomarker that captures peripheral vascular pathophysiology relevant to ABI-defined PAD,” the researchers wrote.
The researchers said they don’t think their new model should replace ABI testing. Instead, they envision PPG screening as a complementary tool that could serve to identify patients earlier that might need further vascular evaluation.
The team said prospective deployment studies are already underway to evaluate performance in clinical settings and across additional reference standards, including toe pressure measurements, ultrasound imaging, and angiography. Additional research will also gauge performance in consumer-grade environments, including smartphones and wearable devices, and assess how the screening tool functions in broader patient populations outside specialized vascular clinics.
“If we can catch PAD early enough to prevent a limb amputation, that would be the ultimate impact: preserving limb function, reducing mortality, and addressing barriers in underserved populations,” Ramsis said.
The post PPG-Derived Digital Biomarker Developed for Peripheral Artery Disease Detection appeared first on Inside Precision Medicine.
Antibody-Drug Conjugate Shows Activity in Hard-to-Treat Uterine Cancer
A Phase II clinical trial led by researchers at Yale School of Medicine and Yale Cancer Center has found that the antibody-drug conjugate sacituzumab govitecan, also known as Trodelvy, demonstrated encouraging clinical activity in patients with recurrent uterine cancer who had already exhausted several standard treatment options.
The findings, published in Clinical Cancer Research, suggest the therapy could become an important new option for patients with advanced endometrial cancer after chemotherapy and immunotherapy stop working.
A difficult disease to treat after relapse
Endometrial cancer is the most common gynecologic cancer in the United States, and rates continue to rise worldwide. While recent advances in immunotherapy have improved treatment for some patients, options remain limited once the disease returns after platinum-based chemotherapy or checkpoint inhibitor therapy.
Patients with recurrent disease often face poor outcomes, particularly those with aggressive tumor types such as uterine serous carcinoma and carcinosarcoma. Standard second-line chemotherapies typically produce modest response rates and short-lived disease control.
Researchers therefore wanted to investigate whether sacituzumab govitecan could improve outcomes in this challenging setting.
How the drug works
Sacituzumab govitecan belongs to a newer class of targeted therapies known as antibody-drug conjugates, or ADCs. These drugs combine an antibody that recognizes cancer cells with a chemotherapy payload designed to destroy them.
In this case, the therapy targets Trop-2, a protein commonly overexpressed in several aggressive cancers, including many uterine tumors. Attached to the antibody is SN-38, the active metabolite of irinotecan, a well-known chemotherapy drug.
By delivering chemotherapy directly to Trop-2–expressing cancer cells, researchers hope to increase anti-tumor activity while limiting damage to healthy tissue.
The drug is already approved for metastatic breast cancer and urothelial cancer, but remains investigational in uterine cancer.
Trial included heavily pretreated patients
The study enrolled 50 patients with recurrent or persistent endometrial cancer between 2020 and 2024. All participants had previously received platinum-based chemotherapy, and many had also undergone treatment with immune checkpoint inhibitors such as pembrolizumab or dostarlimab.
The study population represented a particularly difficult-to-treat group. Most patients had aggressive tumor histologies, including serous carcinoma, carcinosarcoma, or grade 3 endometrioid disease. Patients had received a median of two prior treatment regimens, with some undergoing as many as four lines of therapy before entering the study.
Encouraging responses and survival data
The trial met its primary endpoint, achieving an objective response rate of 28%. Two patients experienced complete responses with no detectable cancer remaining, while another 12 patients achieved partial responses with substantial tumor shrinkage.
In total, more than 70% of evaluable patients experienced some degree of tumor reduction during treatment. The study also reported durable responses, with a median response duration of 9.3 months. Several patients were still responding at the time of analysis.
Median progression-free survival reached 5.5 months, while median overall survival was 17.5 months in this heavily pretreated population.
Researchers also noted that responses were observed across multiple tumor subtypes rather than being limited to one specific histology.
“The results of our Investigator Initiated Trial complement and extend the TROPiCS-03 Trial results by demonstrating significant clinical activity of SG not only against the most common histological types of uterine cancer (endometrioid tumors) but also in patients harboring biologically aggressive endometrial tumors such as uterine serous carcinoma and carcinosarcoma,” said Alessandro Santin, MD, the study’s lead author.
Side effects remained manageable
As expected with potent cancer therapies, treatment-related side effects were common. The most frequent severe toxicities included neutropenia, anemia, fatigue, diarrhea, and febrile neutropenia.
However, investigators reported that most adverse events were manageable using supportive care measures such as growth factor support, anti-diarrheal medications, hydration, and dose adjustments. No treatment-related deaths were reported during the trial.
Looking ahead
The researchers cautioned that the study was relatively small and lacked a randomized comparison arm. Nevertheless, the results add to growing evidence supporting sacituzumab govitecan in advanced endometrial cancer, particularly for patients who have limited options remaining after standard therapies fail.
A larger international Phase III study is already underway to compare the drug directly against standard chemotherapy in patients with recurrent endometrial cancer following platinum chemotherapy and immunotherapy.
The team also highlighted future possibilities for combining the therapy with immunotherapy approaches, particularly because the drug’s chemotherapy payload may help stimulate anti-tumor immune responses.
“This is a major bench-to-bedside accomplishment for patients with uterine cancer,” Santin said.
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<![CDATA[Psychiatry faces surging stress-driven illness as psychedelics, lifestyle medicine, and biomarkers reshape precision diagnosis and care.]]>
Complication Risk Classification in Children and Adolescents With Type 1 Diabetes: Interpretable Machine Learning Study Based on Saudi Clinical Guidelines
Background: Complication risks in children and adolescents with type 1 diabetes (T1D) can lead to serious health outcomes if not detected early. Despite the availability of clinical data, there remains a gap in interpretable tools that support risk stratification in this age group, particularly in alignment with local clinical guidelines. Objective: The purpose of this study is to develop a clinically interpretable model that classifies the risk levels of T1D complications—acute, chronic, and low—using real-world data and expert clinical rules derived from the Saudi Diabetes Clinical Practice Guidelines. Methods: A pediatric T1D dataset comprising of 306 patients was preprocessed through structured cleaning and feature engineering. Risk labels were constructed using Saudi Diabetes Clinical Practice Guidelines–derived rules. Feature selection was performed using a hybrid approach that combined the SHAP (Shapley Additive Explanations) analysis with exhaustive feature selection. A decision tree model was trained and optimized via cross-validation, using the -score as the primary performance metric. Results: The final model achieved a high mean -score of 0.9876 with a low variance of 0.0189, using only 5 clinical features: BMI, hypoglycemia, disease duration, hemoglobin A, and impaired glucose metabolism. These features were consistently ranked as the most influential. The resulting decision tree offered a transparent logic path, enhancing its clinical interpretability and usability. Conclusions: This study demonstrates that a simple and interpretable model, guided by national clinical guidelines, can effectively predict the risk levels of T1D complications in children and adolescents. Its strong performance, clarity, and reliance on a small number of clinically meaningful features make it a promising candidate for integration into clinical decision support systems. This supports a shift toward predictive and personalized diabetes care.
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