Acquisition of durable insulin-producing cells from human adipose tissue-derived mesenchymal stem cells as a foundation for cell- based therapy of diabetes mellitus.

This study aimed to identify the suitable induction protocol to produce highly qualified insulin producing cells (IPCs) from human adipose tissue derived stem cells (ADSCs) and evaluate the efficacy of the most functionally IPCs in management of diabetes mellitus (DM) in rats. The ADSCs were isolated and characterized according to the standard guidelines. ADSCs were further induced to be IPCs in vitro using three different protocols. The success of trans-differentiation was assessed in vitro through analysis of pancreatic endocrine genes expression, and insulin release in response to glucose stimulation. Then, the functionalization of the generated IPCs was evaluated in vivo. The in vitro findings revealed that the laminin-coated plates in combination with insulin-transferrin-selenium, B27, N2, and nicotinamide could efficiently up-regulate the expression of pancreatic endocrine genes. The in vivo study indicated effectual homing of the PKH-26-labelled IPCs in the pancreas of treated animals. Moreover, IPCs infusion in diabetic rats induced significant improvement in the metabolic parameters and prompted considerable up-regulation in the expression of the pancreatic related genes. The regenerative effect of infused IPCs was determined through histological examination of pancreatic tissue. Conclusively, the utilization of laminin-coated plates in concomitant with extrinsic factors promoting proliferation and differentiation of ADSCs could efficiently generate functional IPCs.

Employment Decisions of Newly Graduated Occupational Therapists.

Introduction. Employment decision-making is essential for understanding workforce trends. Current occupational therapy workforce research describes distribution disparities of occupational therapists within geographic locations, services such as acute care or community health, and private or public sectors. New graduates of occupational therapy programs are critical to meeting the demand and distribution disparities of occupational therapy services in British Columbia. However, recent employment decision-making of new occupational therapy graduates has not been well studied. Purpose. This study aimed to examine factors that influence newly graduated occupational therapists' employment decisions. Methods. This descriptive study sampled 122 occupational therapists who were registered in one province and graduated from a Canadian occupational therapy program between 2017 and 2022. Data was collected through an online survey about intrinsic factors, extrinsic factors, and past fieldwork experiences that affected participants' employment decision-making. Descriptive data analysis was used to organize participants' responses. Findings. Results identified that work-life balance and mentorship were the highest rated factors that influenced participants' current and first employment respectively. Participants agreed that the variety and number of placements they had as students were more influential to their employment decisions than the length of the fieldwork education. Conclusion. This study identified the intrinsic and extrinsic factors in employment choices that may influence recruitment, retention, and workplace planning of new graduates.

Determining Factors in the Implementation of Biosecurity Measures by Hospital Nurses in Piura, Peru.

Nosocomial infections are a significant cause of morbidity, mortality, and increased treatment costs in hospitals. This study aimed to analyze the factors determining the implementation of biosafety measures by the nursing staff of four hospitals in Piura via a structural equation modeling (SEM) approach. A total of 215 nurses from various hospitals in the region participated by completing an online survey. The results demonstrated that extrinsic factors (FEX) positively influence the implementation of biosafety measures (BIOM) (ß = 0.319 ***), as do intrinsic factors (FINT) (ß = 0.520 **). Furthermore, intrinsic factors mediate the relationship between extrinsic factors and the implementation of biosafety measures (ß = 0.443 ***). In conclusion, this study provides a deeper understanding of biosafety dynamics in healthcare settings and lays the groundwork for the development of customized interventions and ongoing training programs that ensure the optimal implementation of biosafety measures in hospitals.

Bottom-up effects drive the dynamic of an Antarctic seabird predator-prey system.

Understanding how populations respond to variability in environmental conditions and interspecific interactions is one of the biggest challenges of population ecology, particularly in the context of global change. Although many studies have investigated population responses to climate change, very few have explicitly integrated interspecific relationships when studying these responses. In this study, we aimed to understand the combined effects of interspecific interactions and environmental conditions on the demographic parameters of a prey-predator system of three sympatric seabird populations breeding in Antarctica: the south polar skua (Catharacta maccormicki) and its two main preys during the breeding season, the Adélie penguin (Pygoscelis adeliae) and the emperor penguin (Aptenodytes forsteri). We built a two-species integrated population model (IPM) with 31 years of capture-recapture and count data and provided a framework that made it possible to estimate the demographic parameters and abundance of a predator-prey system in a context where capture-recapture data were not available for one species. Our results showed that predator-prey interactions and local environmental conditions differentially affected south polar skuas depending on their breeding state of the previous year. Concerning prey-predator relationships, the number of Adélie penguin breeding pairs showed a positive effect on south polar skua survival and breeding probability, and the number of emperor penguin dead chicks showed a positive effect on the breeding success of south polar skuas. In contrast, there was no evidence for an effect of the number of south polar skuas on the demography of Adélie penguins. We also found an important impact of sea ice conditions on both the dynamics of south polar skuas and Adélie penguins. Our results suggest that this prey-predator system is mostly driven by bottom-up processes and local environmental conditions.

Factors influencing amyloid fibril formation.

Protein aggregation is a complex process with several stages that lead to the formation of complex structures and shapes with a broad variability in stability and toxicity. The aggregation process is affected by various factors and environmental conditions that disrupt the protein's original state, including internal factors like mutations, expression levels, and polypeptide chain truncation, as well as external factors, such as dense molecular surroundings, post-translation modifications, and interactions with other proteins, nucleic acids, small molecules, metal ions, chaperones, and lipid membranes. During the aggregation process, the biological activity of an aggregating protein may be reduced or eliminated, whereas the resulting aggregates may have the potential to be immunogenic, or they may have other undesirable properties. Finding the cause(s) of protein aggregation and controlling it to an acceptable level is among the most crucial topics of research in academia and biopharmaceutical companies. This chapter aims to review intrinsic pathways of protein aggregation and potential extrinsic variables that influence this process.

Advocating for Generalizability: Accepting Inherent Variability in Translation of Animal Research Outcomes.

Advancing scientific discovery requires investigators to embrace research practices that increase transparency and disclosure about materials, methods, and outcomes. Several research advocacy and funding organizations have produced guidelines and recommended practices to enhance reproducibility through detailed and rigorous research approaches; however, confusion around vocabulary terms and a lack of adoption of suggested practices have stymied successful implementation. Although reproducibility of research findings cannot be guaranteed due to extensive inherent variables in attempts at experimental repetition, the scientific community can advocate for generalizability in the application of data outcomes to ensure a broad and effective impact on the comparison of animals to translation within human research. This report reviews suggestions, based upon work with National Institutes of Health advisory groups, for improving rigor and transparency in animal research through aspects of experimental design, statistical assessment, and reporting factors to advocate for generalizability in the application of comparative outcomes between animals and humans.

Impact of animal origin of milk, processing technology, type of product, and price on the Boursin cheese choice process: Insights of a discrete choice experiment and eye tracking.

Boursin is a versatile semisoft cheese that can be made with different types of milk. While widely distributed in the European and North American markets, Boursin is produced to a limited extent in Brazil despite its commercial potential. This scenario encourages consumer-oriented product development studies by facilitating data collection with less bias and fewer product preconceptions, thus favoring the investigation of technological aspects of commercial interest. This study evaluates Brazilians' perceptions regarding different versions of Boursin cheese, with the aim of gaining a better understanding of the factors related to choosing cheese. Four attributes related to cheese production were evaluated at three different levels using two discrete choice experiments: one with eye tracking (n = 20) and another without (n = 312). These attributes included "type of processing" (evaluating pasteurization, ohmic heating, and preparation with raw milk), "animal origin of milk" (cow, goat, or buffalo milk), "type of product" (traditional, light, and lactose-free versions), and "price" (10.99, 13.99, and 16.99 BRL). Information regarding processing with ohmic heating did not affect the probability of Boursin being chosen, suggesting that consumers are open to using this emerging technology in Boursin cheese. However, information on being made with goat, buffalo, and raw milk negatively impacted the probability of choice, along with the price of 16.99 BRL. The frequency of cheese consumption and the level of health concerns also affected the probability of choosing the product. PRACTICAL APPLICATION: Identifying the relationship between extrinsic attributes presented on the Boursin cheese label and the consumer's choice process can aid the communication process with the target audience and reveal how some technological issues of interest to manufacturers are perceived. This study indicates how information regarding the animal origin of the milk (cow, goat, and buffalo), the type of processing (pasteurization, ohmic heating, and raw milk), the version of the product (traditional, light, and lactose-free), and the price affect the consumer choice process. The results provide insights that can be applied to product processing and designing labels.

Predicting student-teacher self-directed learning using intrinsic and extrinsic factors: a Theory of Planned Behavior adoption.

Introduction: This study set out to develop a model that illustrates the causal relationship between factors influencing Thai student-teacher self-directed learning (SDL). To achieve this, the authors analyzed and applied the Theory of Planned Behavior (TPB) to investigate the role of family support, teacher support, friend support, fellow students, and the university in influencing SDL. Methods: The research used a sample of 468 student-teachers from five academic majors randomly selected from the King Mongkut's Institute of Technology Ladkrabang (KMITL) Bachelor of Industrial Education Program during the 2021 academic year. The authors developed a questionnaire which was evaluated from both a panel of experts and a 30 student-teacher pilot test which found that item reliability was acceptable. LISREL 9.10 was used to analyze the data from the study's structural equation model path analysis. Results: The results revealed that all the causal variables in the model positively influenced SDL, explaining the variance of influencing factors on SDL (R2) at 51%. SDL comprised five variables, when ranked in order of importance these were fellow students (FSt), teacher support (TS), family support (FS), friend support (FrS), and their university (Uni). The study also highlighted issues concerning each student-teacher's learning time management ability and their perception of the university's ability/willingness to allow each individual to choose their course, thus enhancing their SDL learning ability skills. Discussion: It was speculated that some university educators even today perceive SDL as an adult education tool which they perceive is not appropriate at the university level. The authors also felt that for younger student-teachers that the COVID-19 medical emergency limited teacher/student/university interaction, thus contributing to student misconceptions about support availability. This study contributes significantly to the literature by investigating how TPB intrinsic and extrinsic factors impact a university student's self-directed learning.

Intrinsic and extrinsic factors affecting axillary odor variation. A comprehensive review.

Humans produce odorous secretions from multiple body sites according to the microbiomic profile of each area and the types of secretory glands present. Because the axilla is an active, odor-producing region that mediates social communication via the sense of smell, this article focuses on the biological mechanisms underlying the creation of axillary odor, as well as the intrinsic and extrinsic factors likely to impact the odor and determine individual differences. The list of intrinsic factors discussed includes sex, age, ethnicity, emotions, and personality, and extrinsic factors include dietary choices, diseases, climate, and hygienic habits. In addition, we also draw attention to gaps in our understanding of each factor, including, for example, topical areas such as the effect of climate on body odor variation. Fundamental challenges and emerging research opportunities are further outlined in the discussion. Finally, we suggest guidelines and best practices based on the factors reviewed herein for preparatory protocols of sweat collection, data analysis, and interpretation.

Intrinsic and extrinsic factors determining natural killer cell fate: Phenotype and function.

Natural killer (NK) cells are derived from hematopoietic stem cells. They belong to the innate lymphoid cell family, which is an important part of innate immunity. This family plays a role in the body mainly through the release of perforin, granzyme, and various cytokines and is involved in cytotoxicity and cytokine-mediated immune regulation. NK cells involved in normal immune regulation and the tumor microenvironment (TME) can exhibit completely different states. Here, we discuss the growth, development, and function of NK cells in regard to intrinsic and extrinsic factors. Intrinsic factors are those that influence NK cells to promote cell maturation and exert their effector functions under the control of internal metabolism and self-related genes. Extrinsic factors include the metabolism of the TME and the influence of related proteins on the "fate" of NK cells. This review targets the potential of NK cell metabolism, cellular molecules, regulatory genes, and other mechanisms involved in immune regulation. We further discuss immune-mediated tumor therapy, which is the trend of current research.

Extrinsic and intrinsic modulators of inflammation-resolution signaling in heart failure.

Chronic and uncleared inflammation is the root cause of various cardiovascular diseases. Fundamentally, acute inflammation is supportive when overlapping with safe clearance of inflammation termed resolution; however, if the lifestyle-directed extrinsic factors such as diet, sleep, exercise, or physical activity are misaligned, that results in unresolved inflammation. Although genetics play a critical role in cardiovascular health, four extrinsic risk factors-unhealthy processed diet, sleep disruption or fragmentation, sedentary lifestyle, thereby, subsequent stress-have been identified as heterogeneous and polygenic triggers of heart failure (HF), which can result in several complications with indications of chronic inflammation. Extrinsic risk factors directly impact endogenous intrinsic factors, such as using fatty acids by immune-responsive enzymes [lipoxygenases (LOXs)/cyclooxygenases (COXs)/cytochromes-P450 (CYP450)] to form resolution mediators that activate specific resolution receptors. Thus, the balance of extrinsic factors such as diet, sleep, and physical activity feed-forward the coordination of intrinsic factors such as fatty acids-enzymes-bioactive lipid receptors that modulates the immune defense, metabolic health, inflammation-resolution signaling, and cardiac health. Future research on lifestyle- and aging-associated molecular patterns is warranted in the context of intrinsic and extrinsic factors, immune fitness, inflammation-resolution signaling, and cardiac health.

Factors that cause women with osteoporosis to fall.

Objective: To analyze and compare intrinsic and extrinsic factors that cause falls among women receiving treatment for osteoporosis. Subjects and methods: A cross-sectional study of women ≥50 years receiving treatment for osteoporosis. Participants filled out questionnaires (demographic characteristics), and researchers took anthropometric measurements of bone mineral density, handgrip strength (HGS), ankle range of motion (ROM), and gait speed (GS). We also evaluated the Timed Up and Go Test (TUGT), Five Times Sit-to-Stand Test (SST), and Falls Efficacy Scale-International (FES-I) and investigated the extrinsic factors for falls. Results: We included 144 participants (71.6 [8.3 years]), who reported 133 falls. We classified participants into a non-faller group (NFG; 0 falls, n=71, 49.5%), a faller group (FG; 1 fall, n=42, 28.9%), and a recurrent-faller group (RFG; more than 1 fall, n=31, 21.5%). Most patients had an increased risk of falling according to the TUGT, SST, reduced ankle ROM, and GS (P<.005 for all). FES-I was associated with sporadic and recurrent falls. For the multivariate analysis, the number of falls was influenced by the presence of ramps (RR 0.48, 95% CI, 0.26-0.87, P=.015), uneven surfaces (RR 1.6, 95% CI. 1.05-2.43, P=.028), and antislippery adhesive on stairs (RR 2.75, 95% CI, 1.77-4.28, P<.001). Conclusion: Patients receiving treatment for osteoporosis are influenced by intrinsic and extrinsic factors that cause falls. Lower-limb strength and power-discriminated participants at a higher risk of falls, but extrinsic factors varied. Only uneven floors and antislippery adhesives on stairs were associated with increased frequency of falls.

Unveiling the Localized Exciton-Based Photoluminescence of Manganese Doped Cesium Zinc Halide Nanocrystals.

Lead-free metal halide nanocrystals (NCs) have aroused increasing attention due to their unique optoelectronic properties based on localized excitons (LEs). However, the vital influencing factors for the LEs based photoluminescence (PL) are still not well-understood due to the coupling of various intrinsic and extrinsic factors of the NCs. Herein, by engineering the phase, size, morphology, and chemical composition, we are able to decouple the intrinsic and extrinsic factors of manganese doped cesium zinc-halide NCs. We found both the intrinsic metal-halide coordination field and the extrinsic crystal defects have significant influences on the LEs' recombination and energy transfer processes, and hence determine the PL efficiency. Unlike for the free excitons (FEs) based PL, the phase as well as the crystal morphology do not play major roles for the LEs based PL. This work provides a new insight for the study of LE dynamics of metal halide NCs.

What happens when nanoparticles encounter bacterial antibiotic resistance?

Bacterial resistance to antibiotics has become a widespread concern, and poses serious environmental and global health problems. Lots of studies have demonstrated that engineered nanoparticles (NPs) can significantly affect bacterial antibiotic resistance; however, whether NPs promote or inhibit antibiotic resistance remains a complex and well-debated issue. This will constrain environmental antibiotic resistance gene contamination and clinical bacterial resistance problems, resulting in unclear and poorly targeted treatment efficacy. To better understand the relationship between NPs and antibiotic resistance, this review systematically summarizes and reanalyzes published data on the effect of NPs on bacterial antibiotic resistance and related mechanisms. The effects of intrinsic properties of NPs, such as size, concentration, functional groups, and extrinsic properties of NPs on the development of antibiotic resistance were dissected. This review will provide a better understanding of the effects of increasingly released NPs in different environments on bacterial resistance and underlines the direction for employing NPs to control the dissemination of antibiotic resistance genes in the environment. Next, how NPs affect intracellular and extracellular antibiotic resistance needs in-depth exploration. Besides, alternative treatments of NPs and antibiotics in therapy will be a future trend for combating antibiotic resistance, and the follow-up emphasis should determine their dose effects and potential mechanism. This study will expand our understanding of the biosafety of nanomaterials and provides a theoretical reference to guide the proper application of nanomaterials or technologies to environmental pollution control and clinical treatment.

Changes in the Current Patterns of Beef Consumption and Consumer Behavior Trends-Cross-Cultural Study Brazil-Spain-Turkey.

This cross-cultural study aimed to determine the main factors behind potential changes in eating habits by analyzing changes in the patterns of beef consumption currently observed in Brazil, Spain, and Turkey. To achieve this aim, 412 regular beef consumers from Brazil, 407 from Spain, and 424 from Turkey answered a self-administered questionnaire. The study surveyed the effects of economic factors, switching from beef to other sources of protein, aspects of credence, health-related concerns, the influence of lifestyle on beef consumption patterns, and purchasing decision factors. The most important factors that changed consumer behavior and resulted in a decrease in consumption, mostly among Brazilian and Turkish consumers, were the economics and accessibility of the products. Beef was replaced by other alternative sources of protein that were likewise derived from animals. The consumers whose purchasing intentions were most significantly influenced by credence factors (e.g., indiscriminate use of agricultural products, substandard animal welfare requirements, among others) were Brazilian and Turkish and, to a lesser degree, Spanish consumers. Lifestyle factors (e.g., consumption of out-of-home meals, available time to cook, among others) were demonstrated to alter consumption patterns and therefore must be carefully considered by the industry, taking into account cultural differences and consumer needs. The population under investigation considered that eating beef had no impact on their health.

What are the impetuses Behind E-health applications' self-management services' ongoing adoption by health community participants?

Over the past 20 years, the identification of interventions related to healthcare management has been greatly facilitated by improvements in the well-being and health of the entire population. However, regardless of the positive developments in smart health applications and e-health research, there are two important gaps, (1) the role of gamification variables in the continued use of eHealth applications has not been adequately assessed, and (2) the extent to which people's perception of the continued use of e-health applications is encouraged through habit. Customers and companies can derive considerable value from exploring E-Health applications' health self-management services. Accordingly, estimating such services' ongoing adoption by customers is aimed for in this research, with habits, intrinsic and extrinsic variables incorporated into a study model which is then tested. This paper examined perceived autonomy, perceived competence, perceived relatedness has positively related to enjoyment and habit. Reward has positively related to perceived autonomy and continued to use. Enjoyment and Habit have positively associated with the decision to continue to use in e-Health Apps. 269 individuals who have used Chinese e-health applications comprised the data collection sample, being reached via an online questionnaire. Data analysis was undertaken using Partial Least Squares Structural Equation Modelling (PLS-SEM). It was found that the ongoing adoption of e-health self-management services was perpetuated to a greater extent by intrinsic variables; in terms of strategizing for companies' e-services, the results can inform this process.

Paediatric career decision: a literature review of motivational factors.

Unless decision-makers for the future paediatric workforce are aware of different factors that influence the career choices of candidates, they may not be able to meet the needs of this major specialty. Paediatricians should be perceptive, effective communicators and endlessly patient with children. In this article, we conducted a thorough literature search to explore factors affecting career choices among undergraduate and postgraduate students who choose paediatrics or paediatric subspecialties. We assessed the similarities and differences in decision-making in paediatric, medicine, surgery and orthopaedic career contexts to help the candidates in ranking their career options. The authors found that both intrinsic and extrinsic factors shape the career choices of those seeking to work in paediatrics or paediatric subspecialties. A well-structured career development curriculum and clinical experience are considered the most important extrinsic factors, whereas personal characteristics of the candidate and career needs are considered the most important intrinsic factors. These factors may vary across specialties, and even between different subspecialties within the same major specialty. Some factors are considered very important, while others are deemed less so in comparison. The role of mentoring in career selection is crucial. It has been documented in a sizable body of literature that residents are inspired to pursue the careers of their mentors. Paediatrics is no exception. The decision to pursue a subspecialty training is complex and is affected by multiple factors. Those engaged in managing the workforce of the future in the field of paediatrics must familiarise themselves with the intrinsic and extrinsic factors that affect the candidates' career choices.

Factors that cause women with osteoporosis to fall

ABSTRACT Objectives: To analyze and compare intrinsic and extrinsic factors that cause falls among women receiving treatment for osteoporosis. Subjects and methods: A cross-sectional study of women ≥50 years receiving treatment for osteoporosis. Participants filled out questionnaires (demographic characteristics), and researchers took anthropometric measurements of bone mineral density, handgrip strength (HGS), ankle range of motion (ROM), and gait speed (GS). We also evaluated the Timed Up and Go Test (TUGT), Five Times Sit-to-Stand Test (SST), and Falls Efficacy Scale-International (FES-I) and investigated the extrinsic factors for falls. Results: We included 144 participants (71.6 [8.3 years]), who reported 133 falls. We classified participants into a non-faller group (NFG; 0 falls, n = 71, 49.5%), a faller group (FG; 1 fall, n = 42, 28.9%), and a recurrent-faller group (RFG; more than 1 fall, n = 31, 21.5%). Most patients had an increased risk of falling according to the TUGT, SST, reduced ankle ROM, and GS (P < .005 for all). FES-I was associated with sporadic and recurrent falls. For the multivariate analysis, the number of falls was influenced by the presence of ramps (RR 0.48, 95% CI, 0.26-0.87, P = .015), uneven surfaces (RR 1.6, 95% CI. 1.05-2.43, P = .028), and antislippery adhesive on stairs (RR 2.75, 95% CI, 1.77-4.28, P < .001). Conclusion: Patients receiving treatment for osteoporosis are influenced by intrinsic and extrinsic factors that cause falls. Lower-limb strength and power-discriminated participants at a higher risk of falls, but extrinsic factors varied. Only uneven floors and antislippery adhesives on stairs were associated with increased frequency of falls.

Factors Influencing Motivation and Work Engagement of Healthcare Professionals.

Background: Low level of health professionals' work motivation is a critical challenge for countries' health care system. A survey of ministries of health in many countries showed that low motivation was seen as the second most important health workforce problem after staff shortages. Objective: The aim of the study was to examine in detail the factors which can affect motivation and work engagement, to assess the motivation levels of personnel working in public hospitals and to identify any differences between the various categories of healthcare professionals employed at the 1st Regional Health Authority of Attica. Methods: Frederick Herzberg's motivation-hygiene theory was used as the theoretical framework. Twelve phrases were used that correspond to intrinsic and extrinsic motivating factors, namely achievement, recognition, nature of work, responsibility, advancement, growth, organizational policies, supervision, interpersonal relationships, working conditions, salary and job security. Phrases 1-6 covered the internal motivators and 7-12 correspond to the external. Additional questions were added covering the socio-demographic characteristics of respondents. Results: The response rate was 81.95% and 3,278 questionnaires were collected. Findings suggest that extrinsic motivation factors have slightly higher mean scores (MS=8.30) than intrinsic motivation factors (7.81). The role of factors like salary (9.31), organizational policies (8.91), growth (8.89) and job security (8.86) was significant. However, every category of hospital staff is affected in a different way and degree by each factor. In periods of crisis, the need of extrinsic factors of motivation increased. Conclusions: Providing a motivating environment for employees becomes more fundamental in the healthcare system. Motivation of healthcare employees was affected by factors related to supervision, financial benefits, job training and growth. Efforts should be made to provide such benefits to health employees as appropriate especially, to those who did not get any such benefits. Officially recognizing best performance is suggested.

Lineage plasticity in prostate cancer: Looking beyond intrinsic alterations.

Emergence of small cell prostate cancer is linked to the plasticity of tumour cells and avoidance of environmental pressures. This process is thought to be reversable, however to-date evidence of this has been demonstrated in small-cell prostate cancer. To study the plasticity of prostate tumours, we look to clinical cohorts of patients covering the spectra of malignancy subtypes and utilise in vitro and in vivo models of disease progression. Current models have assisted in the understanding of the extremities of this plasticity, elucidating internal mechanisms and adaptations to stressors through transition to altered cell states. By interrogating the tumour microenvironment and earlier time points, we are beginning to form a deeper understanding of the full spectra of tumour plasticity. It could be proffered that this deeper understanding will lead to better patient outcome, with earlier interventions more likely to reverse plasticity and prevent trans-differentiation to the aggressive, small cell phenotype.