tbuckley/cabot-search huggingface dataset:
Social prescribing in the USA: emerging learning and opportunities
Authors: Rachel Marshall, Alexandra Bradbury, Nicole Morgan, Katrina Pineda, Daniel Hayes, Alexandra Burton, Jill Sonke, Daisy Fancourt
Journal: The Lancet Public Health (2025)

The global prevalence of chronic diseases and high costs of health care are complex challenges that are driving countries to focus on addressing the social determinants of health and downstream social needs. These challenges require innovative health-care practices that integrate disease prevention, treatment, and management with salutogenic initiatives to promote population health. Many countries have turned to social prescribing as a promising approach. Social prescribing connects people with non-clinical support and services within their communities. While social prescribing has more commonly been adopted in countries with government-funded national health services, in this Viewpoint, we share learning from examples in the USA. We argue that social prescribing in the USA is unique given the heterogeneity of the country and its health systems, and that this aspect influences programme activities, target-populations, and models. These examples offer valuable lessons about the barriers and enablers to implementing social prescribing in different contexts, including privatised health-care systems. Ultimately, we call upon US stakeholders to recognise the benefits that social prescribing could bring to public health and take action to support its development. We also invite stakeholders from other countries to consider learnings from the USA and how social prescribing can be successfully implemented in their contexts.
Elotuzumab in Combination With Dose Reduced <scp>IMiDs</scp> and Dexamethasone for <scp>AL</scp> Amyloidosis Patients With Relapsed/Refractory Plasma Cell Dyscrasia and Advanced Organ Involvement
Authors: Tobias Dittrich, Timon Hansen, Christoph R. Kimmich, Kaya Veelken, Anna Jauch, Marc S. Raab, Carsten Müller‐Tidow, Ute Hegenbart, Stefan O. Schönland
Journal: American Journal of Hematology (2025)
Use of the Xpert Bladder Cancer Monitor Urinary Biomarker Test for Guiding Cystoscopy in High-grade Non–muscle-invasive Bladder Cancer: Results from the Randomized Controlled DaBlaCa-15 Trial
Authors: Thomas Dreyer, Simone Brandt, Knud Fabrin, Nessn Azawi, Juan Luis Vásquez, Andreas Ernst, Lars Dyrskjøt, Jørgen Bjerggaard Jensen
Journal: European Urology (2025)

Urinary biomarker tests have long been suggested as a noninvasive alternative to current cystoscopy-based follow-up of high-grade non-muscle-invasive bladder cancer (NMIBC) to reduce both morbidity and costs. However, the clinical impact of urinary biomarker tests remains uncertain owing to a lack of randomized trials. In this randomized noninferiority trial, we evaluated the impact of alternating a urinary biomarker test (Xpert Bladder Cancer Monitor, XBCM) with cystoscopy in the intervention arm as a method for reducing the number of cystoscopies during follow-up of patients with high-grade NMIBC. Patients in the control arm underwent cystoscopy at all follow-up visits. The primary outcome was comparison of the risk of recurrence-free survival in terms of high-grade NMIBC, muscle-invasive bladder cancer, or metastatic urothelial carcinoma between the study arms. In total, 43 high-grade recurrences were detected, 22 in the intervention arm and 21 in the control arm. The risk difference for high-grade recurrence between the study arms was 0.08% (95% confidence interval -7.2% to 7.4%). Two pTa high-grade recurrences were missed by the XBCM test. The number of cystoscopies performed was 1029 cystoscopies in the control arm and 445 in the intervention arm. An anticipatory positive effect was observed, with XBCM positivity observed before recurrences were visible on cystoscopy. The findings are limited by a lower-than-expected rate of recurrence in both study arms. Alternating cystoscopy with XBCM reduced the number of follow-up cystoscopies for high-grade NMIBC without affecting detection of any recurrence. The long-term oncological safety of this strategy needs to be validated over longer follow-up.
Use of 4CMenB vaccine in the control of an outbreak of serogroup B invasive meningococcal disease in an elderly care home, England, November 2023
Authors: Emma J Heymer, Stephen A Clark, Helen Campbell, Sonia Ribeiro, Lloyd Walsh, Jay Lucidarme, Xilian Bai, Tom Irving, Anna Hoad, Jaime Morgan, Ray Borrow, Shamez N Ladhani
Journal: Eurosurveillance (2025)

In November 2023, a cluster of two invasive meningococcal disease (IMD) cases caused by serogroup B Neisseria meningitidis (MenB) occurred in elderly residents (≥ 70 years) of a dementia care home in England. An epidemiological investigation was conducted and public health actions, including infection control measures and antibiotic chemoprophylaxis, were implemented to prevent further cases. Nasopharyngeal swabbing before chemoprophylaxis identified three meningococcal carriers, including two carrying the outbreak strain, highlighting the importance of immediate antibiotic prophylaxis in such settings. Microbiological investigations showed that the outbreak strain belonged to the sequence type (ST)-9316 complex, potentially covered by the 4CMenB vaccine. Although 4CMenB is licensed for children and adults, there are no safety or reactogenicity data on use in older adults (≥ 65 years). Given the severity of IMD, residents (64–95 years) and staff (18–72 years) were offered 4CMenB for longer-term protection, with daily diary cards to monitor side effects. In total, 30 residents and 35 of 47 staff received the first dose, with completed diary cards for 26 residents and 32 staff. Twenty-six residents and 28 staff received the second dose, and all completed diary cards. Elderly residents reported fewer and less severe side effects after each dose than younger staff.
Sociodemographic inequalities in the epidemiology and vaccine uptake within a large outbreak of measles in Birmingham, England, 2023 to 2024
Authors: Hannah Jary, Adam Pullen, David Howett, Erjola Hani, Shakeel Suleman, Lisa Byrne, Emma Booth, Richard Puleston, Vanessa Saliba, Colin NJ Campbell, Carol Chatt
Journal: Eurosurveillance (2025)

Measles disproportionately affects under-vaccinated communities, and inequalities in vaccination coverage exist in the United Kingdom (UK). In Birmingham, England, 406 confirmed measles cases were notified to the UK Health Security Agency between 13 October 2023 and 12 April 2024. Public health case management system data and primary care vaccination data were used to describe the epidemiology of the outbreak. Cases had a median age of 5.5 years (interquartile range (IQR): 1–13); 53% (214/406) were male, 45% (183/406) female and sex was unknown for 2% (9/406). Most cases (89%; 362/406) were unvaccinated. While 78% (315/406) of cases occurred in the city’s most deprived areas (quintile 1), none did in the least deprived. The measles rate per 100,000 was 47.6 in quintile 1 vs 13.8 in quintile 3. Across ethnicities, the rate was 86.3 in Black African vs 10.8 in White British. Increases in vaccination rates between the outbreak period and an equivalent prior non-outbreak period seemed higher in most deprived populations (0.5% in quintile 1 vs 0.3% in quintiles 5). Variations, however, were observed between ethnic groups. In this large outbreak, measles disproportionately affected individuals from socioeconomically deprived backgrounds and ethnic minorities. In underserved communities, continued tailored services and vaccinations are required.
Community surveillance after detection of poliovirus in the environment in London, United Kingdom, October 2022 to April 2023
Authors: Thomas Rowland, Robin Gopal, Monika Patel, Cristina Celma, Colin NJ Campbell, Nicholas Machin, Scott Taylor, Shauni-lea Graham, Kathryn Harris, Spiro Pereira, Vanessa Saliba, Maria Zambon
Journal: Eurosurveillance (2025)

Background Vaccine-derived polioviruses (VDPVs) continue to circulate internationally, causing sporadic cases and outbreaks of paralytic polio in countries certified as polio-free. In 2022, sustained detection of type 2 VDPVs was reported in environmental surveillance samples collected from London. Genetic mutations indicative of loss of attenuation of virulence were observed, consistent with community transmission events over several months. Aim We aimed to determine the extent of geographical spread of transmission in an area of environmental poliovirus detection. Methods We implemented an opportunistic, cross-sectional survey in areas where environmental surveillance indicated sustained VDPV transmission between October 2022 and April 2023. Residual stool samples taken from children &lt; 16 years presenting to primary or secondary healthcare were examined for enteroviruses, including poliovirus. Methods for poliovirus detection recommended by the World Health Organization, including virus isolation in cell culture, PCR and molecular characterisation, were applied to residual stool material on a daily basis with real-time clinical reporting. Results We examined 1,251 stool samples from 1,051 children presenting to healthcare with illness over a 6-month period. A range of enteroviruses from groups A, B and C were found, but no poliovirus was detected. Documented polio vaccination coverage was high, between 95% and 98% in under 5-year-olds. Conclusion Poliovirus was not widespread in the area of environmental poliovirus isolation. Opportunistic poliovirus testing of residual stool samples taken from children seeking healthcare was feasible and can be implemented rapidly in areas where poliovirus circulation is suspected, although untargeted sampling may not adequately capture populations at highest risk.
Seroprevalence against measles, Austria, stratified by birth years 1922 to 2024
Authors: David N Springer, Christian Borsodi, Jeremy V Camp, Monika Redlberger-Fritz, Heidemarie Holzmann, Michael Kundi, Judith H Aberle, Karin Stiasny, Lukas Weseslindtner
Journal: Eurosurveillance (2025)

Background Vaccination programmes initiated in the early 1970s reduced the incidence of measles in Austria, which resulted in the interruption of endemic measles virus (MeV) circulation and the achievement of elimination status in 2018. However, large outbreaks occurred in 2023 and 2024. Aim By assessing MeV-specific IgG antibody levels, we analysed if immunity recently declined due to the COVID-19 pandemic, vaccine-induced immunity waned over long term or immunity gaps already pre-existed in the population. Methods We determined anti-MeV antibody levels in a retrospective dataset of 56,360 diagnostic samples (from 50,754 individuals) collected 2010–2024 and correlated antibody cutoffs to titres from a live-virus neutralisation test. Results Individuals born before 1970 (n = 15,007) had antibody levels &gt; 3,000 IU/L, persisting into higher age, and &lt; 2% (n = 300) of them were seronegative. In contrast, individuals born after 1990 (n = 12,778) displayed seronegativity rates of 13–20% and lower median antibody concentrations in seropositive individuals (449–773 IU/L). In these individuals, antibody levels decreased noticeably between the ages of 2 and 10 years but remained stable between those aged 10 and 30 years. There was no significant difference in seronegativity rates at the age of 12–24 months in children born 2016–2019 and 2020–2022 (the years of the COVID-19 pandemic). Conclusion In Austria, there are significant immunity gaps in individuals born after 1970, which pre-existed before the COVID-19 pandemic. Thus, young and middle-aged populations not immune against measles should be vaccinated to counteract a further decline of immunity at the population level and prevent outbreaks whenever MeV is imported.
Persistence of major socio-economic inequalities in childhood measles–mumps–rubella vaccination coverage and timeliness under vaccination mandates, France, 2015 to 2024
Authors: Dimitri Scronias, Lisa Fressard, Laure Fonteneau, Valérie Guagliardo, Pierre Verger
Journal: Eurosurveillance (2025)

Introduction Since the late 2000s, several major measles epidemics have occurred in Europe, including France. In 2017, the French Health Ministry extended from three to 11 the number of mandatory childhood vaccines required for preschool and primary school admission; these included the vaccine against measles, mumps and rubella (MMR). Aim Our aim was to assess if this measure helped to improve MMR vaccine timeliness (VT) or reduce socioeconomic inequalities in MMR vaccine coverage. Methods A nationwide study of three birth cohorts (2015, 2017, 2019) followed up 2.1 million children for 48 months to assess the course of the timeliness of MMR vaccine dispensation, before and after it became mandatory in France (January 2018). Data came from the French national health insurance fund drug reimbursement database. Results Despite improvements from 2015 to 2019, pharmacies dispensed MMR vaccines late for 33% of children in the 2019 cohort (mean cumulative delay compared with recommended dates: 7.1 months). Vaccines for children from low-income families were dispensed later (mean delay of at least +1 month) than those from higher-income families. The 2019 cohort did not reach the 95% WHO target of two MMR doses at 24 months of age, nor at 48 months. Discussion With measles intensifying worldwide, these vaccination delays and inequalities may contribute to the resurgence of epidemics. In addition to vaccination mandates, an ambitious public health policy is needed to reduce inequalities in access to vaccination and to improve parents’ vaccine acceptance through educational strategies.
Promoting retinal ganglion cell regeneration with targeted liposome-based delivery of MHY1485 for optic nerve repair
Authors: Bingqing Luo, Tingting Cheng, Ying Xiang, Shengkai Sun, Yuanshan Liu, Jincong Yan, Yajie Zhang, Yi Cao, Xingzhu Liu, Renjun Pei
Journal: Journal of Controlled Release (2025)
Spatial hepatocyte plasticity of gluconeogenesis during the metabolic transitions between fed, fasted and starvation states
Authors: Junichi Okada, Austin Landgraf, Alus M Xiaoli, Li Liu, Maxwell Horton, Victor L Schuster, Fajun Yang, Simone Sidoli, Yunping Qiu, Irwin J Kurland, Carolina Eliscovich, Kosaku Shinoda, Jeffrey E Pessin
Journal: Nature Metabolism (2025)
Can genomic analysis actually estimate past population size?
Authors: Janeesh K Bansal, Richard A Nichols
Journal: Trends in Genetics (2025)

Genomic data can be used to reconstruct population size over thousands of generations, using a new class of algorithms [sequentially Markovian coalescent (SMC) methods]. These analyses often show a recent decline in Ne (effective size), which at face value implies a conservation or demographic crisis: a population crash and loss of genetic diversity. This interpretation is frequently mistaken. Here we outline how SMC methods work, why they generate this misleading signal, and suggest simple approaches for exploiting the rich information produced by these algorithms. In most species, genomic patterns reflect major changes in the species' range and subdivision over tens or hundreds of thousands of years. Consequently, collaboration between geneticists, palaeoecologists, palaeoclimatologists, and geologists is crucial for evaluating the outputs of SMC algorithms.
Typology of the ecological impacts of biological invasions
Authors: Laís Carneiro, Boris Leroy, César Capinha, Corey J A Bradshaw, Sandro Bertolino, Jane A Catford, Morelia Camacho-Cervantes, Jamie Bojko, Gabriel Klippel, Sabrina Kumschick, Daniel Pincheira-Donoso, Jonathan D Tonkin, Brian D Fath, Josie South, Eléna Manfrini, Tad Dallas, Franck Courchamp
Journal: Trends in Ecology & Evolution (2025)
Abstract LB294: Mechanism of tumor-selective inhibition of dimeric RAF by a Type 1 RAF inhibitor
Authors: Mathieu Desaunay, Tara L. Peters, Beau Baars, Bijaya Gaire, Ana Orive-Ramos, Li Ren, Joseph P. Lyssikatos, Stuart A. Aaronson, Evripidis Gavathiotis, Stefan D. Gross, Poulikos I. Poulikakos
Journal: Cancer Research (2025)

Abstract Over a third of human tumors are driven by deregulated RAS/MAPK signaling, frequently by mutations in RAS or BRAF. First generation RAF inhibitors bind in the Type 1.5 mode (αC-OUT/DFG-IN) and are effective in inhibiting monomeric BRAF(V600X), while inducing paradoxical RAF and MAPK activation in contexts where RAF signals as dimer, including wild-type and RAS-Mutant (RAS-MUT) settings. Thus, these inhibitors are only active against BRAF(V600X), and paradoxical MAPK activation in normal cells enables vertical MAPK-targeting combinations with MEK or EGFR antagonists. These combinations improve both efficacy and tolerability, as they additively suppress MAPK in tumor cells, while they restore physiological levels of MAPK signaling in normal cells. To target cancers driven by dimeric RAF, including RAS-MUT tumors, Type 2 (αC-IN/DFG-OUT) RAF inhibitors have been developed that bind both RAF monomers and dimers. These drugs inhibit RAF in all contexts, including normal cells, with minimal MAPK activation. However, Type 2 RAF inhibitors showed modest results as single agents, and their subsequent combination with MEK inhibitors led to increased efficacy but also enhanced toxicities due to MAPK pathway suppression in normal tissue. Here we characterized ELV-3111, a novel potent and selective Type 1 (αC-IN/DFG-IN) RAF inhibitor with broad and potent activity in various RAS-MUT models, both in cells and in vivo, similar to Type 2 RAF inhibitors. However, unlike Type 2 inhibitors, ELV-3111 induced pronounced paradoxical MAPK hyperactivation selectively in normal cells and tissues in vivo, a phenomenon we successfully modeled in cells. Using an array of biochemical and in-cell target engagement assays, we discovered that MAPK hyperactivation by Type 1 RAF inhibitors occurs via a RAS-dependent allosteric mechanism that is distinct from the described paradoxical activation mechanism of Type 1,5 inhibitors. Thus, the unique mechanism of action of Type 1 RAF inhibitors enables vertical MAPK-targeting combinations that are expected to be safer and more effective for patients with cancers driven by dimeric RAF, compared to current treatments. Citation Format: Mathieu Desaunay, Tara L. Peters, Beau Baars, Bijaya Gaire, Ana Orive-Ramos, Li Ren, Joseph P. Lyssikatos, Stuart A. Aaronson, Evripidis Gavathiotis, Stefan D. Gross, Poulikos I. Poulikakos. Mechanism of tumor-selective inhibition of dimeric RAF by a Type 1 RAF inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB294.
Abstract LB476: Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis
Authors: Reuben S. Harris
Journal: Cancer Research (2025)

Abstract Mutations in somatic cells are inflicted by both extrinsic and intrinsic sources and contribute over time to cancer. Tobacco smoke contains chemical carcinogens that have been causatively implicated with cancers of the lung and head &amp; neck. APOBEC family DNA cytosine deaminases have emerged as endogenous sources of mutation in cancer, with hallmark mutational signatures (SBS2/SBS13) that often co-occur in tumors of tobacco smokers with an equally diagnostic mutational signature (SBS4). Here we challenge the dogma that mutational processes are thought to occur independently and with additive impact by showing that 4-nitroquinoline 1-oxide (NQO), a model carcinogen for tobacco exposure, sensitizes cells to APOBEC3B (A3B) mutagenesis and leads to synergistic increases in both SBS2 mutation loads and oral carcinomas in vivo. NQO-exposed/A3B-expressing mice exhibit twice as many head &amp; neck lesions as carcinogen-exposed wildtype animals. This increase in carcinogenesis is accompanied by a synergistic increase in mutations from APOBEC signature SBS2, but not from NQO signature SBS4. Interestingly, a large proportion of A3B-catalyzed SBS2 mutations occurs as strand-coordinated pairs within 32 nucleotides of each other in transcribed regions, suggesting a mechanism in which removal of NQO-DNA adducts by nucleotide excision repair exposes short single-stranded DNA tracts to enzymatic deamination. These highly enriched pairs of APOBEC signature mutations are termed didyma (Greek for twins) and are mechanistically distinct from other types of clustered mutation (omikli and kataegis). Computational analyses of lung and head &amp; neck tumor genomes show that both APOBEC mutagenesis and didyma are elevated in cancers from smokers compared to non-smokers. APOBEC signature mutations and didyma are also elevated in normal lung tissues in smokers prior to cancer initiation. Collectively, these results indicate that DNA adducting mutagens in tobacco smoke can amplify DNA damage and mutagenesis by endogenous APOBEC enzymes and, more broadly, suggest that mutational mechanisms can interact synergistically in both cancer initiation and promotion. Citation Format: Reuben S. Harris. Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB476.
Abstract SY11-01: Ferroptosis and cancer metabolism: History, mechanisms, and therapeutic applications
Authors: Brent R. Stockwell
Journal: Cancer Research (2025)

Abstract Ferroptosis is form of cell death tightly integrated with metabolism and driven by peroxidation of specific lipids. I will discuss the history, key regulators, recent emerging mechanisms, and therapeutic applications of controlling ferroptosis. We identified an unusual species of lipid that is a key driver of ferroptosis; our studies linking ferroptosis to metabolism have enabled design of precision, therapeutic diets that promote ferroptosis in some cancer models. We found that we can promote ferroptosis in specific cancers by making dietary changes that enhance lipid peroxidation and limit the repair capacity of cancer cells. In addition, we found that these ferroptosis-promoting dietary changes enhance the response of cancer cells to pro-ferroptosis small molecule drug candidates, such as GPX4 inhibitors. We have this found that specific pairing of drugs with rationally designed dietary changes can substantially improve therapeutic effects in animal models. Citation Format: Brent R. Stockwell. Ferroptosis and cancer metabolism: History, mechanisms, and therapeutic applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr SY11-01.