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1.
Health Soc Care Deliv Res ; : 1-15, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38721979

RESUMEN

Background: Liaison mental health services provide mental health care to patients in acute hospital settings. Evaluation of liaison services is challenging due to their heterogeneous organisation and delivery, high case throughput and varied patient case mix. We aimed to link routinely collected National Health Service data from secondary care settings, chosen for their service characteristics, to data from primary care to evaluate hospital-based liaison mental health services in England. Methods: We planned to compare patients referred to hospital-based liaison services with comparable patients in the same hospital not referred to liaison services and comparable patients in hospitals without any liaison services. We designed and enacted a methodology to link data from: (1) Hospital Episode Statistics, a database controlled by the National Health Service Digital and (2) ResearchOne, a primary care database controlled by The Phoenix Partnership. Results: Obtaining approvals for the steps prespecified in the methodological protocol took 907 days. Enactment following approvals took 385 days. Data supplied from Hospital Episode Statistics contained 181,063 patients from 6 hospitals (mean = 30,177, standard deviation = 28,875.86) who matched the inclusion and exclusion criteria. Data supplied from ResearchOne contained 33,666 (18.6%) of these patients from the 6 hospitals (mean = 5611, standard deviation = 5206.59). Discussion: Time required for approvals and enactment was attributable to slowness of data handling processes within each data holder and to resolution of technical and organisational queries between them. Variation in number of patients for which data was supplied between databases and between hospitals was attributable to coding inconsistencies and to the limited intersection of patient populations between databases and variation in recording practices between hospitals. Conclusion: Although it is technically feasible to link primary and secondary care data, the current system is challenging, complicated, unnecessarily bureaucratic, time consuming and costly. This limits the number of studies that could be conducted with these rich data sources. Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number 13/58/08.


Liaison mental health services are based in acute general hospitals and provide assessment and treatment for people who have both physical and mental health problems. Our aim was to use routinely collected National Health Service data to find out whether general hospital patients referred to liaison mental health services have improved outcomes, compared with patients not referred to liaison services, and comparable patients in hospitals where there are no liaison services. The main outcomes were less time spent in hospital and fewer re-admissions to hospital following discharge. We tried to link data from routine National Health Service sources for hospital and primary care, to compare patients referred to liaison mental health services with similar people in each hospital who had not been referred, and similar people in hospitals without any liaison services at all. We planned to find out how long these people stayed in hospital, whether they were re-admitted and how much was their healthcare cost was. We experienced significant difficulties in being able to link the National Health Service data from the different organisations we approached. The whole process was extremely complex, and a delay in one part of the process resulted delays in other parts. We eventually had to abandon the research without obtaining any meaningful data, although the lessons we learnt will be useful for other researchers, so they can avoid experiencing similar problems. Routinely collected National Health Service data from primary care and secondary care can be linked using the approaches we tried, but we were unable to complete the process within the time frame of the research programme, even with time extensions. Current processes need to be streamlined and standardised with designated clear response times for the different organisations.

2.
PLoS One ; 19(5): e0302746, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38728340

RESUMEN

BACKGROUND: Long-term health conditions can affect labour market outcomes. COVID-19 may have increased labour market inequalities, e.g. due to restricted opportunities for clinically vulnerable people. Evaluating COVID-19's impact could help target support. AIM: To quantify the effect of several long-term conditions on UK labour market outcomes during the COVID-19 pandemic and compare them to pre-pandemic outcomes. METHODS: The Understanding Society COVID-19 survey collected responses from around 20,000 UK residents in nine waves from April 2020-September 2021. Participants employed in January/February 2020 with a variety of long-term conditions were matched with people without the condition but with similar baseline characteristics. Models estimated probability of employment, hours worked and earnings. We compared these results with results from a two-year pre-pandemic period. We also modelled probability of furlough and home-working frequency during COVID-19. RESULTS: Most conditions (asthma, arthritis, emotional/nervous/psychiatric problems, vascular/pulmonary/liver conditions, epilepsy) were associated with reduced employment probability and/or hours worked during COVID-19, but not pre-pandemic. Furlough was more likely for people with pulmonary conditions. People with arthritis and cancer were slower to return to in-person working. Few effects were seen for earnings. CONCLUSION: COVID-19 had a disproportionate impact on people with long-term conditions' labour market outcomes.


Asunto(s)
COVID-19 , Empleo , Humanos , COVID-19/epidemiología , COVID-19/economía , Reino Unido/epidemiología , Masculino , Femenino , Empleo/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Pandemias/economía , SARS-CoV-2/aislamiento & purificación , Adulto Joven , Adolescente , Encuestas y Cuestionarios , Anciano , Renta/estadística & datos numéricos
3.
Toxicol Ind Health ; : 7482337241253310, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748851

RESUMEN

The water extractability and acute aquatic toxicity of seven aliphatic diisocyanate-based prepolymer substances were investigated to determine if lesser reactivity of the aliphatic isocyanate groups, as well as increased ionization potential of the expected (aliphatic amine-terminated) polymeric hydrolysis products, would influence their aquatic behavior compared to that of previously investigated aromatic diisocyanate-based prepolymers. At loading rates of 100 and 1,000 mg/L, only the substances having log Kow ≤9 exhibited more than 1% extractability in water, and a maximum of 66% water extractability was determined for a prepolymer having log Kow = 2.2. For the more hydrophobic prepolymer substances (log Kow values from 18-37), water extractability was negligible. High-resolution mass spectrometric analyses were performed on the water-accommodated fractions (WAF) of the prepolymers, which indicated the occurrence of primary aliphatic amine-terminated polymer species having backbones and functional group equivalent weights aligned to those of the parent prepolymers. Measurements of reduced surface tension and presence of suspended micelles in the WAFs further supported the occurrence of these surface-active cationic polymer species as hydrolysis products of the prepolymers. Despite these characteristics, the water-extractable hydrolysis products were practically non-toxic to Daphnia magna. All of the substances tested exhibited 48-h EL50 values of >1,000 mg/L, with one exception of EL50 = 157 mg/L. The results from this investigation support a grouping of the aliphatic diisocyanate-based prepolymers as a class of water-reactive polymer substances having predictable aquatic exposure and a uniformly low hazard potential, consistent with that previously demonstrated for the aromatic diisocyanate-based prepolymers.

4.
BMC Cancer ; 24(1): 533, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671382

RESUMEN

BACKGROUND: In Saudi Arabia, approximately one-third of colorectal cancer (CRC) patients are diagnosed at an advanced stage. Late diagnosis is often associated with a worse prognosis. Understanding the risk factors for late-stage presentation of CRC is crucial for developing targeted interventions enabling earlier detection and improved patient outcomes. METHODS: We conducted a retrospective cohort study on 17,541 CRC patients from the Saudi Cancer Registry (1997-2017). We defined distant CRCs as late-stage and localized and regional CRCs as early-stage. To assess risk factors for late-stage CRC, we first used multivariable logistic regression, then developed a decision tree to segment regions by late-stage CRC risk, and finally used stratified logistic regression models to examine geographical and sex variations in risk factors. RESULTS: Of all cases, 29% had a late-stage diagnosis, and 71% had early-stage CRC. Young (< 50 years) and unmarried women had an increased risk of late-stage CRC, overall and in some regions. Regional risk variations by sex were observed. Sex-related differences in late-stage rectosigmoid cancer risk were observed in specific regions but not in the overall population. Patients diagnosed after 2001 had increased risks of late-stage presentation. CONCLUSION: Our study identified risk factors for late-stage CRC that can guide targeted early detection efforts. Further research is warranted to fully understand these relationships and develop and evaluate effective prevention strategies.


Asunto(s)
Neoplasias Colorrectales , Estadificación de Neoplasias , Sistema de Registros , Humanos , Arabia Saudita/epidemiología , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Factores de Riesgo , Adulto , Diagnóstico Tardío/estadística & datos numéricos , Factores Sexuales , Detección Precoz del Cáncer
5.
Cancer Discov ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38552005

RESUMEN

Tumor-associated macrophages are transcriptionally heterogeneous, but the spatial distribution and cell interactions that shape macrophage tissue roles remain poorly characterized. Here, we spatially resolve five distinct human macrophage populations in normal and malignant human breast and colon tissue and reveal their cellular associations. This spatial map reveals that distinct macrophage populations reside in spatially segregated micro-environmental niches with conserved cellular compositions that are repeated across healthy and diseased tissue. We show that IL4I1+ macrophages phagocytose dying cells in areas with high cell turnover and predict good outcome in colon cancer. In contrast, SPP1+ macrophages are enriched in hypoxic and necrotic tumor regions and portend worse outcome in colon cancer. A subset of FOLR2+ macrophages is embedded in plasma cell niches. NLRP3+ macrophages co-localize with neutrophils and activate an inflammasome in tumors. Our findings indicate that a limited number of unique human macrophage niches function as fundamental building blocks in tissue.

6.
Sci Rep ; 14(1): 5284, 2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38438436

RESUMEN

Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.


Asunto(s)
Inteligencia Artificial , Neoplasias de la Próstata , Humanos , Masculino , Patólogos , Próstata , Biopsia
7.
Age Ageing ; 53(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38520142

RESUMEN

BACKGROUND: Falls are common in older adults and can devastate personal independence through injury such as fracture and fear of future falls. Methods to identify people for falls prevention interventions are currently limited, with high risks of bias in published prediction models. We have developed and externally validated the eFalls prediction model using routinely collected primary care electronic health records (EHR) to predict risk of emergency department attendance/hospitalisation with fall or fracture within 1 year. METHODS: Data comprised two independent, retrospective cohorts of adults aged ≥65 years: the population of Wales, from the Secure Anonymised Information Linkage Databank (model development); the population of Bradford and Airedale, England, from Connected Bradford (external validation). Predictors included electronic frailty index components, supplemented with variables informed by literature reviews and clinical expertise. Fall/fracture risk was modelled using multivariable logistic regression with a Least Absolute Shrinkage and Selection Operator penalty. Predictive performance was assessed through calibration, discrimination and clinical utility. Apparent, internal-external cross-validation and external validation performance were assessed across general practices and in clinically relevant subgroups. RESULTS: The model's discrimination performance (c-statistic) was 0.72 (95% confidence interval, CI: 0.68 to 0.76) on internal-external cross-validation and 0.82 (95% CI: 0.80 to 0.83) on external validation. Calibration was variable across practices, with some over-prediction in the validation population (calibration-in-the-large, -0.87; 95% CI: -0.96 to -0.78). Clinical utility on external validation was improved after recalibration. CONCLUSION: The eFalls prediction model shows good performance and could support proactive stratification for falls prevention services if appropriately embedded into primary care EHR systems.


Asunto(s)
Fracturas Óseas , Hospitalización , Humanos , Anciano , Estudios Retrospectivos , Fracturas Óseas/diagnóstico , Fracturas Óseas/epidemiología , Fracturas Óseas/prevención & control , Modelos Logísticos
8.
Resuscitation ; : 110168, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38458416

RESUMEN

AIM: To assess patient socio-demographic and disease characteristics associated with the initiation, timing, and completion of emergency care and treatment planning in a large UK-based hospital trust. METHODS: Secondary retrospective analysis of data across 33 months extracted from digitally stored Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) plans within the electronic health record system of an acute hospital trust in England, UK. RESULTS: Data analysed from ReSPECT plans (n = 23,729), indicate an increase in the proportion of admissions having a plan created from 4.2% in January 2019 to 6.9% in September 2021 (mean = 8.1%). Forms were completed a median of 41 days before death (a median of 58 days for patients with capacity, and 21 days for patients without capacity). Do not attempt resuscitation was more likely to be recorded for patients lacking capacity, with increasing age (notably for patients aged over 74 years), being male, having ethnicity recorded as 'Asian or Asian British' or 'Black or Black British', and the absence of multiple disease groups. Having a preferred place of death recorded as 'hospital' led to a five-fold increase in the likelihood of dying in hospital. CONCLUSION: Variation in the initiation, timing, and completion of ReSPECT plans was identified by applying an evaluation framework. Digital storage of ReSPECT plan data presents opportunities for assessing trends and completion of the ReSPECT planning process and benchmarking across sites. Further research is required to monitor and understand any inequity in the implementation of the ReSPECT process in routine care.

9.
J Infect ; 88(3): 106116, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38331329

RESUMEN

OBJECTIVE: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling. METHODS: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC. RESULTS: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors. INTERPRETATION: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings.


Asunto(s)
Hipersensibilidad a las Drogas , Hipersensibilidad , Humanos , Penicilinas/efectos adversos , Antibacterianos/efectos adversos , Estudios de Factibilidad , Pruebas Cutáneas , Hipersensibilidad a las Drogas/diagnóstico , Atención a la Salud
10.
Proc Natl Acad Sci U S A ; 121(8): e2313377121, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38349876

RESUMEN

In recent years, critics of online platforms have raised concerns about the ability of recommendation algorithms to amplify problematic content, with potentially radicalizing consequences. However, attempts to evaluate the effect of recommenders have suffered from a lack of appropriate counterfactuals-what a user would have viewed in the absence of algorithmic recommendations-and hence cannot disentangle the effects of the algorithm from a user's intentions. Here we propose a method that we call "counterfactual bots" to causally estimate the role of algorithmic recommendations on the consumption of highly partisan content on YouTube. By comparing bots that replicate real users' consumption patterns with "counterfactual" bots that follow rule-based trajectories, we show that, on average, relying exclusively on the YouTube recommender results in less partisan consumption, where the effect is most pronounced for heavy partisan consumers. Following a similar method, we also show that if partisan consumers switch to moderate content, YouTube's sidebar recommender "forgets" their partisan preference within roughly 30 videos regardless of their prior history, while homepage recommendations shift more gradually toward moderate content. Overall, our findings indicate that, at least since the algorithm changes that YouTube implemented in 2019, individual consumption patterns mostly reflect individual preferences, where algorithmic recommendations play, if anything, a moderating role.

11.
Trials ; 25(1): 8, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167481

RESUMEN

BACKGROUND: Frailty is common in older age and is characterised by loss of biological reserves across multiple organ systems. These changes associated with frailty mean older people can be vulnerable to sudden, dramatic changes in health because of relatively small problems. Older people with frailty are at increased risk of adverse outcomes including disability, hospitalisation, and care home admission, with associated reduction in quality of life and increased NHS and social care costs. Personalised Care Planning offers an anticipatory, preventative approach to supporting older adults to live independently for longer, but it has not been robustly evaluated in a population of older adults with frailty. METHODS: Following an initial feasibility study, this multi-centre, individually randomised controlled trial aims to establish whether personalised care planning for older people improves health-related quality of life. It will recruit 1337 participants from general practices across Yorkshire and Humber and Mid-Mersey in the North of England. Eligible patients will be aged 65 and over with an electronic frailty index score of 0.21 or above, living in their own homes, without severe cognitive impairment and not in receipt of end-of-life care. Following confirmation of eligibility, informed consent and baseline data collection, participants will be individually randomised to the PeRsOnaliSed care Planning for oldER people with frailty (PROSPER) intervention or usual care in a 2.6:1 allocation ratio. Participants will not be blinded to allocation, but data collection and analysis will be blinded. The intervention will be delivered over 12 weeks by a Personal Independence Co-ordinator worker based within a voluntary sector organisation, Age UK. The primary outcomes are health-related quality of life, measured using both the physical and mental components of the Short-Form 12 Item Health Questionnaire at 12 months after randomisation. Secondary outcomes comprise activities of daily living, self-management capabilities and loneliness, admission to care homes, hospitalisations, and health and social care resource use at 12 months post randomisation. Parallel cost-effectiveness and process evaluations will be conducted alongside the trial. DISCUSSION: The PROSPER study will evaluate the effectiveness and cost-effectiveness of a personalised care planning approach for older people with frailty and inform the process of its implementation. TRIAL REGISTRATION: ISRCTN16123291 .  Registered on  28 August 2020.


Asunto(s)
Actividades Cotidianas , Fragilidad , Humanos , Anciano , Fragilidad/diagnóstico , Fragilidad/terapia , Calidad de Vida , Inglaterra , Encuestas y Cuestionarios , Análisis Costo-Beneficio , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
12.
J Phys Chem C Nanomater Interfaces ; 128(2): 984, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38264432

RESUMEN

[This corrects the article DOI: 10.1021/acs.jpcc.3c04361.].

13.
Br J Health Psychol ; 29(1): 3-19, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37537895

RESUMEN

OBJECTIVES: We aimed to identify psychological factors associated with the use of facemasks in shops in England following removal of legal requirements to do so, and to compare associations with and without legal restrictions. DESIGN: Repeated cross-sectional online surveys (n ≈ 2000 adults) between August 2020 and April 2022 (68,716 responses from 45,682 participants) using quota sampling. METHODS: The outcome measure was whether those who had visited a shop for essentials in the previous seven days reported always having worn a facemask versus sometimes or not at all. Psychological predictor variables included worry, perceived risk and severity of COVID-19 and the perceived effectiveness of facemasks. Socio-demographic variables and measures of clinical vulnerability were also measured. For the period following removal of legal restrictions, multivariable regression was used to assess associations between the primary outcome variable and predictors adjusting for socio-demographic and clinical vulnerability measures. The analysis was repeated including interactions between psychological predictors and presence versus absence of legal restrictions. RESULTS: Worry about COVID-19, beliefs about risks and severity of COVID-19 and effectiveness of facemasks were substantially and independently associated with the use of facemasks. Removal of legal obligations to wear facemasks was associated with a 25% decrease in wearing facemasks and stronger associations between psychological predictors and wearing facemasks. CONCLUSIONS: Legal obligations increase rates of wearing a facemask. Psychological factors associated with wearing a facemask could be targets for interventions aiming to alter rates of wearing a facemask. These interventions may be more effective when there are no legal obligations to wear a face covering in place.


Asunto(s)
COVID-19 , Adulto , Humanos , Máscaras , Pandemias , Estudios Transversales , Inglaterra
14.
Addiction ; 119(2): 225-235, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37724014

RESUMEN

BACKGROUND AND AIMS: Inadequate reporting of smoking cessation intervention trials is common and leads to significant challenges for researchers. The aim of this study was to tailor CONSORT (Consolidated Standards of Reporting Trials)-SPI (Social and Psychological Interventions) guidelines to improve reporting of trials of behavioural interventions to promote smoking cessation. METHOD: Informed by missing data from the IC-SMOKE (Intervention and Comparison group support provided in SMOKing cEssation) systematic review project, this study used a multi-stage Delphi process to examine which items could be added or modified to improve the reporting of smoking cessation trials. The first stage involved an on-line survey of 17 international experts in smoking cessation and trial methodology voting on the importance of items for inclusion in the updated guidelines. This was followed by a face-to-face expert consensus meeting attended by 15 of these experts, where the final inclusion and exclusion of new items and modifications were agreed upon. A nine-point Likert scale was used to establish consensus, with suggested modifications requiring agreement of 75% or more. Disagreements in the first stage were presented again at the second stage for discussion and a second round of voting. Only items which reached the threshold for agreement were included. RESULTS: The experts agreed on the inclusion of 10 new items and the specification of 12 existing items. This included modifications that could apply to trials more widely (e.g. the rationale for the comparator), but also modifications that were very specific to smoking cessation trials (e.g. the reporting of smoking cessation outcomes). CONCLUSIONS: A Delphi study has developed a modified CONSORT-SPI guideline (CONSORT-SPI-SMOKE) to improve the reporting of trials of behavioural interventions to promote smoking cessation.


Asunto(s)
Cese del Hábito de Fumar , Humanos , Terapia Conductista , Consenso , Proyectos de Investigación
16.
JCI Insight ; 9(2)2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-37971878

RESUMEN

Benign prostatic hyperplasia (BPH) is the nodular proliferation of the prostate transition zone in older men, leading to urinary storage and voiding problems that can be recalcitrant to therapy. Decades ago, John McNeal proposed that BPH originates with the "reawakening" of embryonic inductive activity by adult prostate stroma, which spurs new ductal proliferation and branching morphogenesis. Here, by laser microdissection and transcriptional profiling of the BPH stroma adjacent to hyperplastic branching ducts, we identified secreted factors likely mediating stromal induction of prostate glandular epithelium and coinciding processes. The top stromal factors were insulin-like growth factor 1 (IGF1) and CXC chemokine ligand 13 (CXCL13), which we verified by RNA in situ hybridization to be coexpressed in BPH fibroblasts, along with their cognate receptors (IGF1R and CXCR5) on adjacent epithelium. In contrast, IGF1 but not CXCL13 was expressed in human embryonic prostate stroma. Finally, we demonstrated that IGF1 is necessary for the generation of BPH-1 cell spheroids and patient-derived BPH cell organoids in 3D culture. Our findings partially support historic speculations on the etiology of BPH and provide what we believe to be new molecular targets for rational therapies directed against the underlying processes driving BPH.


Asunto(s)
Hiperplasia Prostática , Masculino , Adulto , Humanos , Anciano , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Próstata/metabolismo , Epitelio/metabolismo , Fibroblastos/metabolismo , Perfilación de la Expresión Génica
17.
Artículo en Inglés | MEDLINE | ID: mdl-38110242

RESUMEN

Spatial findings have shaped on our understanding of breast cancer. In this review, we discuss how spatial methods, including spatial transcriptomics and proteomics and the resultant understanding of spatial relationships, have contributed to concepts regarding cancer progression and treatment. In addition to discussing traditional approaches, we examine how emerging multiplex imaging technologies have contributed to the field and how they might influence future research.


Asunto(s)
Neoplasias de la Mama , Proteómica , Humanos , Neoplasias de la Mama/genética , Femenino , Transcriptoma , Progresión de la Enfermedad
18.
J Phys Chem C Nanomater Interfaces ; 127(45): 21915-21929, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38024195

RESUMEN

In nanomechanical photothermal absorption spectroscopy and microscopy, the measured substance becomes a part of the detection system itself, inducing a nanomechanical resonance frequency shift upon thermal relaxation. Suspended, nanometer-thin ceramic or 2D material resonators are innately highly sensitive thermal detectors of localized heat exchanges from substances on their surface or integrated into the resonator itself. Consequently, the combined nanoresonator-analyte system is a self-measuring spectrometer and microscope responding to a substance's transfer of heat over the entire spectrum for which it absorbs, according to the intensity it experiences. Limited by their own thermostatistical fluctuation phenomena, nanoresonators have demonstrated sufficient sensitivity for measuring trace analyte as well as single particles and molecules with incoherent light or focused and wide-field coherent light. They are versatile in their design, support various sampling methods-potentially including hydrated sample encapsulation-and hyphenation with other spectroscopic methods, and are capable in a wide range of applications including fingerprinting, separation science, and surface sciences.

19.
Nat Mater ; 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957268

RESUMEN

Breast cancer becomes invasive when carcinoma cells invade through the basement membrane (BM)-a nanoporous layer of matrix that physically separates the primary tumour from the stroma. Single cells can invade through nanoporous three-dimensional matrices due to protease-mediated degradation or force-mediated widening of pores via invadopodial protrusions. However, how multiple cells collectively invade through the physiological BM, as they do during breast cancer progression, remains unclear. Here we developed a three-dimensional in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces-but not invadopodia-to breach the BM. Forces are generated from a combination of global cell volume expansion, which stretches the BM, and local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results uncover a mechanism by which cells collectively interact to overcome a critical barrier to metastasis.

20.
ACS Photonics ; 10(10): 3730-3739, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37869554

RESUMEN

Understanding light-matter interaction at the nanoscale requires probing the optical properties of matter at the individual nanoabsorber level. To this end, we developed a nanomechanical photothermal sensing platform that can be used as a full spectromicroscopy tool for single molecule and single particle analysis. As a demonstration, the absorption cross-section of individual gold nanorods is resolved from a spectroscopic and polarization standpoint. By exploiting the capabilities of nanomechanical photothermal spectromicroscopy, the longitudinal localized surface plasmon resonance in the NIR range is unraveled and quantitatively characterized. The polarization features of the transversal surface plasmon resonance in the VIS range are also analyzed. The measurements are compared with the finite element method, elucidating the role played by electron surface and bulk scattering in these plasmonic nanostructures, as well as the interaction between the nanoabsorber and the nanoresonator, ultimately resulting in absorption strength modulation. Finally, a comprehensive comparison is conducted, evaluating the signal-to-noise ratio of nanomechanical photothermal spectroscopy against other cutting-edge single molecule and particle spectroscopy techniques. This analysis highlights the remarkable potential of nanomechanical photothermal spectroscopy due to its exceptional sensitivity.

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