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1.
bioRxiv ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38915726

ABSTRACT

Efforts to cure BCR::ABL1 B cell acute lymphoblastic leukemia (Ph+ ALL) solely through inhibition of ABL1 kinase activity have thus far been insufficient despite the availability of tyrosine kinase inhibitors (TKIs) with broad activity against resistance mutants. The mechanisms that drive persistence within minimal residual disease (MRD) remain poorly understood and therefore untargeted. Utilizing 13 patient-derived xenograft (PDX) models and clinical trial specimens of Ph+ ALL, we examined how genetic and transcriptional features co-evolve to drive progression during prolonged TKI response. Our work reveals a landscape of cooperative mutational and transcriptional escape mechanisms that differ from those causing resistance to first generation TKIs. By analyzing MRD during remission, we show that the same resistance mutation can either increase or decrease cellular fitness depending on transcriptional state. We further demonstrate that directly targeting transcriptional state-associated vulnerabilities at MRD can overcome BCR::ABL1 independence, suggesting a new paradigm for rationally eradicating MRD prior to relapse. Finally, we illustrate how cell mass measurements of leukemia cells can be used to rapidly monitor dominant transcriptional features of Ph+ ALL to help rationally guide therapeutic selection from low-input samples.

2.
Qual Health Res ; : 10497323241254253, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857417

ABSTRACT

Healthcare organizations worldwide face challenges in retaining their healthcare workforce, with individual and organizational factors influencing their intentions to leave. This study conducted eight online co-creation workshops and four Delphi sessions to gain qualitative and in-depth insights into job retention interventions, involving healthcare workers, hospital managers, and policymakers. A thematic analysis was conducted, resulting in multiple interventions that were clustered in four pre-defined themes: professional and personal support, education, financial incentives, and regulatory measures. Professional and personal support interventions included regular interprofessional team meetings, leadership training programs, self-scheduling and sabbaticals, support for administrative and non-clinical work, and the provision of psychological counselling. Educational interventions encompassed facilitating development opportunities, periodic evaluations, onboarding, mentorship programs, and peer support groups. Financial incentives included the provision of competitive salaries, adequate infrastructure, extra benefits, transport possibilities, and permanent employment contracts. Regulatory measures addressed the need for complementary legislation across various levels, fixed healthcare worker-to-patient ratio, and instruments to monitor workload. To optimize retention strategies, healthcare organizations should tailor these interventions to address the unique factors influencing their workforce's intentions to leave within their specific context. The study concludes that combining personal and professional support, educational opportunities, financial incentives, and regulatory measures is necessary because there is no one-size-fits-all solution.

3.
Am J Clin Nutr ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38719093

ABSTRACT

BACKGROUND: Infants born moderate-to-late preterm (i.e., 32 wk-35 wk 6 d gestation) are, analogous to those born very preterm, at risk of later obesity, hypertension, and diabetes. Appropriate early life nutrition is key for ensuring optimal growth and body composition, thereby mitigating potential cardiometabolic risks. OBJECTIVES: We aimed to compare growth and body composition between infants born moderate-to-late preterm fed isocaloric but protein- and mineral-enriched postdischarge formula (PDF) or standard term formula (STF) until 6 mo corrected age (CA; i.e., after term equivalent age [TEA]). METHODS: After enrollment (≤7 d postpartum), infants received PDF if (fortified) mother's own milk (MOM) was insufficient. At TEA, those receiving >25% of intake as formula were randomized to either continue the same PDF (n = 47) or switch to STF (n = 50); those receiving ≥75% of intake as MOM (n = 60) served as references. At TEA and 6 mo CA, we assessed anthropometry and body composition using both dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP). RESULTS: Feeding groups had similar gestational age (median [25th percentile;75th percentile]: 34.3 [33.5; 35.1] wk), birthweight (mean ± standard deviation [SD]: 2175 ± 412 g), anthropometry, and body composition at TEA. At 6 mo CA, infants fed PDF had slightly, but significantly, greater length (67.6 ± 2.5 and 66.9 ± 2.6 cm, P < 0.05) and larger head circumference (43.9 ± 1.3 and 43.4 ± 1.5 cm, P < 0.05) compared to infants fed STF. Also, infants fed PDF had higher lean mass (LM) and bone mineral content estimated by DXA (4772 ± 675 and 4502 ± 741 g; 140 ± 20 and 131 ± 23 g, respectively; P < 0.05). ADP estimates, however, were not statistically different between feeding groups. CONCLUSIONS: Infants born moderate-to-late preterm demonstrated modest increases in length, head circumference, LM, and bone mineral content when fed PDF compared to STF for 6 mo after TEA. This trial was registered at the International Clinical Trial Registry Platform as NTR5117 and NTR NL4979.

4.
Fam Syst Health ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38661643

ABSTRACT

BACKGROUND: The aim of this study was to investigate the link between parenting and parents' perspectives on health-related decision making for adolescents. During adolescence, there is a gradual increase in responsibility and autonomy, which influences parenting behavior and child development. Understanding how parenting is associated with parents' views on medical decision making is crucial in the context of the parent-child-physician triad. This study was the first to explore parenting and parents' views on adolescent health care decision making. We compare Belgian and Dutch parents-two countries selected for their different legal frameworks on medical adolescent decision making. METHOD: An online questionnaire surveyed 984 Belgian and 992 Dutch parents (ages 35-55) with at least one child. Analytical methods included t tests, structural equation modeling, and latent profile analysis. RESULTS: Parents considered adolescents to be competent decision makers at 16.7 years old. Dutch parents granted autonomy at younger ages than Belgian parents. Parents with high behavioral expectations granted autonomy to adolescents at higher ages, while those high in autonomy support and punishment granted autonomy at lower ages. When classifying parents into profiles, we distinguished four types: highly permissive, moderately permissive, moderately restrictive, and highly restrictive groups. The majority of the sample was classified into moderately and highly restrictive profiles. CONCLUSION: The study highlighted the importance of providing parents with education and support on adolescent development and autonomy. Parenting practices that encourage autonomy and support open communication between parents and adolescents may contribute to a more trusting and supportive parent-child context for adolescent medical decision making. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

6.
Electrophoresis ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38456383

ABSTRACT

When hospitalized, infants, particularly preterm, are often subjected to multiple painful needle procedures to collect sufficient blood for metabolic screening or diagnostic purposes using standard clinical tests. For example, at least 100 µL of whole blood is required to perform one creatinine plasma measurement with enzymatic colorimetric assays. As capillary electrophoresis-mass spectrometry (CE-MS) utilizing a sheathless porous tip interface only requires limited amounts of sample for in-depth metabolic profiling studies, the aim of this work was to assess the utility of this method for the determination of creatinine in low amounts of plasma using residual blood samples from adults and infants. By using a starting amount of 5 µL of plasma and an injection volume of only 6.7 nL, a detection limit (S/N = 3) of 30 nM could be obtained for creatinine, and intra- and interday precisions (for peak area ratios) were below 3.2%. To shorten the electrophoretic separation time, a multi-segment injection (MSI) strategy was employed to analyze up to seven samples in one electrophoretic run. The findings obtained by CE-MS for creatinine in pretreated plasma were compared with the values acquired by an enzymatic colorimetric assay typically used in clinical laboratories for this purpose. The comparison revealed that CE-MS could be used in a reliable way for the determination of creatinine in residual plasma samples from infants and adults. Nevertheless, to underscore the clinical efficacy of this method, a subsequent investigation employing an expanded pool of plasma samples is imperative. This will not only enhance the method's diagnostic utility but also contribute to minimizing both the amount and frequency of blood collection required for diagnostic purposes.

7.
bioRxiv ; 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38405697

ABSTRACT

Clustering is commonly used in single-cell RNA-sequencing (scRNA-seq) pipelines to characterize cellular heterogeneity. However, current methods face two main limitations. First, they require user-specified heuristics which add time and complexity to bioinformatic workflows; second, they rely on post-selective differential expression analyses to identify marker genes driving cluster differences, which has been shown to be subject to inflated false discovery rates. We address these challenges by introducing nonparametric clustering of single-cell populations (NCLUSION): an infinite mixture model that leverages Bayesian sparse priors to identify marker genes while simultaneously performing clustering on single-cell expression data. NCLUSION uses a scalable variational inference algorithm to perform these analyses on datasets with up to millions of cells. By analyzing publicly available scRNA-seq studies, we demonstrate that NCLUSION (i) matches the performance of other state-of-the-art clustering techniques with significantly reduced runtime and (ii) provides statistically robust and biologically relevant transcriptomic signatures for each of the clusters it identifies. Overall, NCLUSION represents a reliable hypothesis-generating tool for understanding patterns of expression variation present in single-cell populations.

8.
Children (Basel) ; 11(1)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38255422

ABSTRACT

The major focus of this research is the level of awareness among Dutch parents of general patient rights in relation to minors' patient rights. Moreover, this study is intended to highlight the most effective strategies to increase the awareness of general and minor patient rights in the Netherlands. A survey was conducted among 1010 Dutch parents aged between 35 and 55 years who had at least one child. In this study, we described the relationship between the knowledge among parents of general patient rights and their understanding of the patient rights of minors. A significant connection was found between the knowledge levels of general patient rights and the knowledge levels of the patient rights of minors (p < 0.05 [95% CI: 0.019-0.183]). While age and sex (male/female) did not appear to be significant confounders in this association, the educational background of the participants may have played a role. This study provides comprehensive insights into the association between the knowledge of general patient rights and the patient rights of minors among Dutch parents. Furthermore, this study points out that there is a need for focused educational interventions to address specific areas of misunderstanding or uncertainty.

9.
J Child Health Care ; : 13674935231211217, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37885151

ABSTRACT

Alternative family configurations are becoming more prevalent, yet current legislative statutory does not support stepparents in medical decisions for their stepchildren. We investigate opinions of Belgian and Dutch adults regarding inclusion of stepparents in medical decision-making in minors. We make two observations. First, participants wanted stepparents to be involved in cases when medical information had to be shared or informed consent signed. Second, when stepparents object against previously approved medical interventions by a biological parent, respondents were less likely to support stepparents. Participants with stepchildren were likely to favour inclusion of stepparents in decision-making. Overall, our findings indicate that Belgian and Dutch adults view stepparents as potential executive actors in medical decision-making for minors, but not as primary decision-makers. This study is a first step in showing to what extent stepparents could be included in medical information and decision-making regarding stepchildren. We reflect on these findings in light of implications for medical practice and legislative shortcomings.

10.
Int J Occup Med Environ Health ; 36(3): 417-427, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37681429

ABSTRACT

OBJECTIVES: Healthcare systems in European countries, including METEOR partner countries, are faced with the aging population, an increase in costs for innovative technologies and medication, a shortage of health professionals, and inequality in access to healthcare. Presented paper aimed to recognize and compare the functioning of healthcare systems between METEOR partner countries and simultaneously check if the current epidemiological situation of COVID-19 has some relationship with the number of medical staff, yearly gross domestic product, or documented percentage of fully vaccinated people. MATERIAL AND METHODS: In the model of descriptive epidemiological study, available demographic, socioeconomic, and healthcare organizational data in the Netherlands, Belgium, Italy, and Poland were compared to the epidemiological situation of the COVID-19 pandemic (percentage of fully vaccinated people, incidence, and mortality) in all mentioned countries. RESULTS: Obtained data confirmed that the lowest number of physicians, as well as the life expectancy and gross domestic product per capita, is in Poland. Simultaneously, the lower number of medical staff and lower gross domestic product (GDP) correspond to higher mortality due to COVID-19. The percentage of fully vaccinated with the last dose of the primary series was also the lowest in Poland. CONCLUSIONS: Obtained results confirmed that higher mortality due to COVID-19 in METEOR participants' countries is related to a lower number of medical staff and weaker GDP. The worse situation was noted in Poland, a country with problems in the functioning healthcare system, including hospital care and a serious shortage of practicing medical staff. Int J Occup Med Environ Health. 2023;36(3):417-27.


Subject(s)
COVID-19 , Pandemics , Humans , Aged , Belgium , Netherlands , Poland/epidemiology , Hospitals , Italy/epidemiology
11.
Sensors (Basel) ; 23(14)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37514627

ABSTRACT

A digital twin is a computer-based "virtual" representation of a complex system, updated using data from the "real" twin. Digital twins are established in product manufacturing, aviation, and infrastructure and are attracting significant attention in medicine. In medicine, digital twins hold great promise to improve prevention of cardiovascular diseases and enable personalised health care through a range of Internet of Things (IoT) devices which collect patient data in real-time. However, the promise of such new technology is often met with many technical, scientific, social, and ethical challenges that need to be overcome-if these challenges are not met, the technology is therefore less likely on balance to be adopted by stakeholders. The purpose of this work is to identify the facilitators and barriers to the implementation of digital twins in cardiovascular medicine. Using, the Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework, we conducted a document analysis of policy reports, industry websites, online magazines, and academic publications on digital twins in cardiovascular medicine, identifying potential facilitators and barriers to adoption. Our results show key facilitating factors for implementation: preventing cardiovascular disease, in silico simulation and experimentation, and personalised care. Key barriers to implementation included: establishing real-time data exchange, perceived specialist skills required, high demand for patient data, and ethical risks related to privacy and surveillance. Furthermore, the lack of empirical research on the attributes of digital twins by different research groups, the characteristics and behaviour of adopters, and the nature and extent of social, regulatory, economic, and political contexts in the planning and development process of these technologies is perceived as a major hindering factor to future implementation.


Subject(s)
Delivery of Health Care , Technology , Humans , Technology/methods , Delivery of Health Care/methods , Empirical Research , Computer Simulation
12.
Healthcare (Basel) ; 11(13)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37444721

ABSTRACT

The shortage of healthcare workers is a growing concern. The COVID-19 pandemic and retirement wave have accelerated turnover rates. This systematic review aimed to identify and analyse the existing interventions for job retention of healthcare workers, in terms of nurses and physicians, in a hospital setting. A comprehensive search was conducted within three electronic databases, guided by the preferred reporting items for systematic review and meta-analyses (PRISMA) and synthesis without meta-analysis (SWiM) guidelines, this resulted in 55 records that met the inclusion criteria. The intervention outcomes are categorized into substantial themes: onboarding, transition program to a different unit, stress coping, social support, extra staffing, coping with the demands of patient care, work relationships, development opportunities and department resources, job environment, work organization, recruitment approach, and technological innovations. Considering the literature, onboarding programs and mentoring for nurses and physicians are recommended. Additionally, other interventions described in this review could positively affect the retention of nurses and physicians. When selecting an intervention for implementation, managers and human resources should consider the intervention that matches the determinant of intention to leave of their healthcare workers and the hospital's mission, vision, and values. Sharing the success stories of implemented interventions may benefit healthcare organizations.

13.
Proc Natl Acad Sci U S A ; 120(16): e2210418120, 2023 04 18.
Article in English | MEDLINE | ID: mdl-37040401

ABSTRACT

The hypoxia-inducible factor 1-α (HIF-1α) enables cells to adapt and respond to hypoxia (Hx), and the activity of this transcription factor is regulated by several oncogenic signals and cellular stressors. While the pathways controlling normoxic degradation of HIF-1α are well understood, the mechanisms supporting the sustained stabilization and activity of HIF-1α under Hx are less clear. We report that ABL kinase activity protects HIF-1α from proteasomal degradation during Hx. Using a fluorescence-activated cell sorting (FACS)-based CRISPR/Cas9 screen, we identified HIF-1α as a substrate of the cleavage and polyadenylation specificity factor-1 (CPSF1), an E3-ligase which targets HIF-1α for degradation in the presence of an ABL kinase inhibitor in Hx. We show that ABL kinases phosphorylate and interact with CUL4A, a cullin ring ligase adaptor, and compete with CPSF1 for CUL4A binding, leading to increased HIF-1α protein levels. Further, we identified the MYC proto-oncogene protein as a second CPSF1 substrate and show that active ABL kinase protects MYC from CPSF1-mediated degradation. These studies uncover a role for CPSF1 in cancer pathobiology as an E3-ligase antagonizing the expression of the oncogenic transcription factors, HIF-1α and MYC.


Subject(s)
Gene Expression Regulation , Transcription Factors , Humans , Cullin Proteins/metabolism , Hypoxia , Phosphorylation , Protein Serine-Threonine Kinases/metabolism , Transcription Factors/metabolism , Ubiquitin-Protein Ligases/metabolism , Genes, abl , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Cleavage And Polyadenylation Specificity Factor/metabolism
14.
Inquiry ; 60: 469580231159318, 2023.
Article in English | MEDLINE | ID: mdl-36912131

ABSTRACT

The shortage of healthcare workers is a growing problem across the globe. Nurses and physicians, in particular, are vulnerable as a result of the COVID-19 pandemic. Understanding why they might leave is imperative for improving retention. This systematic review explores both the prevalence of nurses and physicians who are intent on leaving their position at hospitals in European countries and the main determinants influencing job retention among nurses and physicians of their respective position in a hospital setting in both European and non-European countries. A comprehensive search was fulfilled within 3 electronic databases on June 3rd 2021. In total 345 articles met the inclusion criteria. The determinants were categorized into 6 themes: personal characteristics, job demands, employment services, working conditions, work relationships, and organizational culture. The main determinants for job retention were job satisfaction, career development and work-life balance. European and non-European countries showed similarities and differences in determinants influencing retention. Identifying these factors supports the development of multifactorial interventions, which can aid the formulation of medical strategies and help to maximize retention.


Subject(s)
COVID-19 , Nursing Staff, Hospital , Physicians , Humans , Personnel Turnover , Pandemics , Health Personnel , Job Satisfaction , Hospitals , Surveys and Questionnaires
15.
Arch Dis Child ; 108(8): 654-658, 2023 08.
Article in English | MEDLINE | ID: mdl-36927621

ABSTRACT

BACKGROUND: Parents are often confronted with a difficult decision when their child falls ill: should they go to the general practitioner (GP) or not? This study aims to describe this process comprehensively in order to allow clinicians to assess the extent to which parents can recognise clinical warning signs and act accordingly. The purpose of this study is to describe parents' decision-making processes when deciding whether or not to consult a GP for their sick child. METHODS: We used a qualitative study design based on semistructured interviews to investigate the decision-making process of 25 parents. Four case scenarios describing a developing illness in a child were presented. RESULTS: Parents' reasons for seeking medical attention could be divided into two main categories. First, non-specific fears lead parents to consult a doctor. Parents were alarmed by the persistence and progression of symptoms, the combination of symptoms or changes in their child's behaviour or they needed reassurance. Second, several specific fears were identified. Sometimes, parents fear a specific disease, while at other times, they are concerned about warning signs. Some parents, however, would not seek medical attention at any decision point even though their child could be in a potentially life-threatening situation. CONCLUSIONS: Although parents make carefully considered decisions on whether or not to consult a doctor, many appear to miss red flags, including more experienced parents. Conversely, some become overly concerned with certain specific symptoms such as fever, and few parents are familiar with self-management strategies.


Subject(s)
Fear , Physicians , Child , Humans , Qualitative Research , Parents , Anxiety/diagnosis
16.
bioRxiv ; 2023 Jan 23.
Article in English | MEDLINE | ID: mdl-36747859

ABSTRACT

High-throughput phenotypic screens leveraging biochemical perturbations, high-content readouts, and complex multicellular models could advance therapeutic discovery yet remain constrained by limitations of scale. To address this, we establish a method for compressing screens by pooling perturbations followed by computational deconvolution. Conducting controlled benchmarks with a highly bioactive small molecule library and a high-content imaging readout, we demonstrate increased efficiency for compressed experimental designs compared to conventional approaches. To prove generalizability, we apply compressed screening to examine transcriptional responses of patient-derived pancreatic cancer organoids to a library of tumor-microenvironment (TME)-nominated recombinant protein ligands. Using single-cell RNA-seq as a readout, we uncover reproducible phenotypic shifts induced by ligands that correlate with clinical features in larger datasets and are distinct from reference signatures available in public databases. In sum, our approach enables phenotypic screens that interrogate complex multicellular models with rich phenotypic readouts to advance translatable drug discovery as well as basic biology.

17.
bioRxiv ; 2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36711936

ABSTRACT

Targeted therapies have revolutionized cancer chemotherapy. Unfortunately, most patients develop multifocal resistance to these drugs within a matter of months. Here, we used a high-throughput phenotypic small molecule screen to identify MCB-613 as a compound that selectively targets EGFR-mutant, EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) cells harboring diverse resistance mechanisms. Subsequent proteomic and functional genomic screens involving MCB-613 identified its target in this context to be KEAP1, revealing that this gene is selectively essential in the setting of EGFR inhibitor resistance. In-depth molecular characterization demonstrated that (1) MCB-613 binds KEAP1 covalently; (2) a single molecule of MCB-613 is capable of bridging two KEAP1 monomers together; and, (3) this modification interferes with the degradation of canonical KEAP1 substrates such as NRF2. Surprisingly, NRF2 knockout sensitizes cells to MCB-613, suggesting that the drug functions through modulation of an alternative KEAP1 substrate. Together, these findings advance MCB-613 as a new tool for exploiting the selective essentiality of KEAP1 in drug-resistant, EGFR-mutant NSCLC cells.

18.
Med Humanit ; 49(1): 17-26, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35545432

ABSTRACT

Artificial intelligence (AI) and machine learning (ML) techniques occupy a prominent role in medical research in terms of the innovation and development of new technologies. However, while many perceive AI as a technology of promise and hope-one that is allowing for more early and accurate diagnosis-the acceptance of AI and ML technologies in hospitals remains low. A major reason for this is the lack of transparency associated with these technologies, in particular epistemic transparency, which results in AI disturbing or troubling established knowledge practices in clinical contexts. In this article, we describe the development process of one AI application for a clinical setting. We show how epistemic transparency is negotiated and co-produced in close collaboration between AI developers and clinicians and biomedical scientists, forming the context in which AI is accepted as an epistemic operator. Drawing on qualitative research with collaborative researchers developing an AI technology for the early diagnosis of a rare respiratory disease (pulmonary hypertension/PH), this paper examines how including clinicians and clinical scientists in the collaborative practices of AI developers de-troubles transparency. Our research shows how de-troubling transparency occurs in three dimensions of AI development relating to PH: querying of data sets, building software and training the model The close collaboration results in an AI application that is at once social and technological: it integrates and inscribes into the technology the knowledge processes of the different participants in its development. We suggest that it is a misnomer to call these applications 'artificial' intelligence, and that they would be better developed and implemented if they were reframed as forms of sociotechnical intelligence.


Subject(s)
Artificial Intelligence , Physicians , Humans
19.
Cancer Res ; 83(3): 441-455, 2023 02 03.
Article in English | MEDLINE | ID: mdl-36459568

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in > 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell-cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC. SIGNIFICANCE: A high-throughput pipeline using multiplex immunofluorescence in pancreatic cancer reveals striking expression subtype intratumoral heterogeneity with implications for therapy selection and identifies co-expressor cells that may serve as intermediates during subtype switching.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Prognosis , Phenotype , RNA , Gene Expression Regulation, Neoplastic , Claudins
20.
J Adolesc Health ; 72(1): 21-26, 2023 01.
Article in English | MEDLINE | ID: mdl-36216676

ABSTRACT

PURPOSE: As children progress through adolescence, they become more independent and more responsible regarding their health. This shift in responsibility from the parents to the adolescent poses a challenge for healthcare professionals who must consider both parties. Pediatricians and other healthcare professionals may encounter problems regarding consent and confidentiality. This study aimed to investigate the opinions of Belgian parents of adolescents concerning cases about confidentiality in adolescent health problems. METHODS: A qualitative methodology with semi-structured interviews and a case-based approach was chosen to answer our study aim. Belgian parents of adolescents were recruited voluntarily; 20 parents were interviewed. Parents' opinions on four different cases regarding confidentiality were obtained. Interviews were audio- and video-recorded and transcribed verbatim. Independent coding of the transcripts was conducted. RESULTS: Parents' opinions differ considerably when asked if a physician has to maintain confidentiality toward the adolescent, depending on the content of the case. Opinions appear underpinned by three factors: trust, responsibility of the different parties, and the etiology of the problem. DISCUSSION: This study shows that the nature, severity, and frequency of the medical issue at hand shape the opinions of parents toward patient confidentiality, on top of the trust and responsibility factors also highlighted in previous work. This is in contrast to the Belgian legislation, which focuses on maturity regardless of context.


Subject(s)
Adolescent Health , Trust , Adolescent , Child , Humans , Parents , Confidentiality , Attitude
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