Understanding the mechanisms of nickel (Ni) uptake by hyperaccumulator plants is essential for advancing sustainable phytomanagement. In this study, saponite materials containing either isotopically natural or 61Ni-enriched Ni were synthesised and applied in RHIZOtest experiments with Odontarrhena chalcidica. The amendments were mixed with two ultramafic soils differing in Ni content, alongside a serpentinite control. Ni bioavailability and uptake were evaluated via elemental and isotopic analysis of plant digests and diffusive gradients in thin films (DGT). Stable isotope spiking with 61Ni allowed tracing of amendment-derived Ni uptake into plant tissues, even though total Ni mass fractions in planted versus unplanted soils did not indicate significant mobilisation during the 14-day growth period. Isotope pattern deconvolution (IPD) revealed clear shifts in Ni isotopic composition in both plant and DGT samples. Tracer uptake was more pronounced in the low Ni soil, with amendment-derived Ni (xamendment) contributing 19.3 ± 5.0% of total Ni in shoots, compared to 7.7 ± 1.8% in the high-Ni soil. In standard solutions containing 50 ng g-1 total Ni, isotope pattern shifts were still detectable at enrichment levels as low as 0.01% xspike (≈ 5 pg g-1 61Ni). The findings demonstrate the sensitivity of stable isotope spiking combined with IPD in the detection of subtle uptake processes, even in short-term experiments. This approach enables the differentiation of various Ni sources in soil-plant systems that would not be achievable with quantification alone, and can thereby provide new insights into how soil mineralogy influences uptake dynamics in metal-hyperaccumulating species.
Classically social prescription interventions focus on loneliness in adulthood, however another transitional stage of the lifespan associated with loneliness is new parenthood. A first-of-its-kind, socially prescribed, creative play programme is being trialed for families with 0-2-year-olds in a deprived ward in the North of England. Yet little is known about the perspectives of key stakeholders on this type of social prescription. This study examined the experience, attitudes and perspectives stakeholders hold around social prescription for families with infants. Individual in depth interview study. This study recruited 12 different stakeholders with practice or policy roles relating to family health and wellbeing, from general practitioners to members of parliament, with different power dynamics and roles to take part in a seven-question semi-structured interview. The interview addressed relationships between stakeholders, how they feel families might value or stigmatize socially prescribed creative play interventions and their thoughts and experiences with social prescription. The interview transcripts were analysed using an inductive descriptive thematic analysis. Three main themes were identified 1) Normalizing a New Offer: Getting it Right the First Time, 2) Barriers to Socially Prescribed Family Intervention and 3) Social Prescription for Complicated Families with Varying Needs. Findings suggest social prescription for families with infants would be welcome, and may relieve strain on our health systems. However, questions remain around how best to deliver such interventions, demonstrating the importance of evaluation to provide evidence to inform wider commissioning and promote sustainability and scaling.
Macrophages are phagocytic immune cells that play a central role in the clearance of apoptotic cells, pathogens and other foreign bodies including particulates that may be injected for therapeutic purposes. Recent work has demonstrated that macrophages that take up microparticles clear pathogens faster; however, the effect of particle uptake on the clearance of apoptotic cells (efferocytosis) remains unclear. Herein, we use cargo-free, non-stimulatory polymeric particles as a tool to investigate how the uptake of such particles affects the efferocytic function of macrophages. Using primary cells isolated from mice, we demonstrate that the uptake of large ∼3 µm sized microparticles, but not smaller 500 nm sized particles, reduces a macrophage's efferocytic ability in vitro. Notably, this effect is pronounced in non-activated M0-type naïve-like macrophages and absent in activated M1- and M2-like macrophages, highlighting polarization-dependent resilience towards particulate stress. Given that efferocytosis contributes to an immunosuppressive tumor microenvironment (TME), we leveraged the phenomenon of microparticle uptake driven lowering of efferocytosis to target apoptotic cell clearance in the TME. In a BALB/C mouse model bearing 4T1 tumors, we demonstrate that direct injection of large microparticles into the tumors results in slower tumor growth. Collectively, these findings reveal that cargo-free, non-stimulatory polymeric microparticles of a specific size impact the efferocytic function of macrophages, which may be utilized to alter the TME for therapeutic purposes.
Primary healthcare (PHC) physicians play a pivotal role in the diagnosis and management of hypertension. While guidelines suggest that blood pressure (BP) should be measured in every patient visit at PHC units, the few studies conducted among PHC physicians report a low ratio of BP measurements in PHC settings. Data on PHC physicians' practices concerning BP measurement in Greece are lacking. This study aimed to investigate the practices of PHC physicians regarding BP measurement in Greece. A cross-sectional web-based survey was conducted among PHC physicians across Greece. A total of 284 PHC physicians completed the questionnaire and 282 responses were included in the analysis, 42.9% male, 92.9% General Practitioners, 89.4% working in the public sector, with a median of 25 (17 - 30) daily patient visits. PHC physicians reported measuring BP in 33.3% (20-50%) of their patients and recommending home BP measurements in 31.1% (SD: 24.3%) of them. Among those who measured BP, 22.3% measured it once, 44.7% measured it twice, and only 21.3% measured it three times, while 54.6% used an electronic upper arm BP monitor. The main barriers reported were high daily patient volume (60.5%), together with limited time available with patients (69.5%), while only 1.3% declared insufficient training. This is the first study in Greece investigating the practices of PHC physicians regarding BP measurements. Our findings underscore the need for targeted interventions to improve BP monitoring practices. Education and motivation of physicians and other primary care team members would be fundamental in addressing the challenge of implementing BP measurement recommendations in clinical practice.
Smoking remains a major issue in the Netherlands. Municipal public health departments (GGDen) and municipalities are playing an increasingly important role in tobacco control policies. However, it is unclear to what extent municipalities actively contribute to tobacco prevention. In recent years, we studied the role of municipal health departments and municipalities in local tobacco control. At the local level, there is a lack of conditions and incentives to prioritize tobacco prevention. To enable municipalities to contribute to national tobacco control goals and prevention, structural funding, clear responsibilities, and measurable targets are needed. Roken blijft een groot probleem in Nederland. We zien dat GGD’en en gemeenten een steeds belangrijkere rol krijgen in het tabaksontmoedigingsbeleid. Het is onduidelijk in hoeverre gemeenten in Nederland concreet bijdragen aan tabaksontmoediging. De afgelopen jaren hebben we onderzoek gedaan naar de rol van GGD’en en gemeenten in lokaal tabaksontmoedigingsbeleid. Op lokaal niveau ontbreken randvoorwaarden en drijfveren om tabaksontmoediging tot een prioriteit te maken. Als we willen dat gemeenten daadwerkelijk een verschil kunnen maken in het behalen van de landelijke doelen op het gebied van tabaksontmoediging en preventie, dan zijn structurele financiering, duidelijke taakstelling en streefwaarden noodzakelijk.
Climate change is increasing the frequency and severity of heatwaves across South Asia, with disproportionate impacts on vulnerable populations. Pregnant and lactating women face heightened health risks due to physiological changes, gendered social responsibilities, and constrained access to adaptive resources. Despite this, women's lived experiences and adaptation practices during pregnancy remain understudied and largely absent from institutional climate responses. This knowledge gap hampers the development of effective, gender-sensitive adaptation policies. This qualitative study, embedded within the Heat in Pregnancy (HiP)-India project, will be conducted in three climatically vulnerable sites: Gurugram (Haryana), Bilaspur (Chhattisgarh), and Puducherry. Guided by a socio-ecological framework, we will conduct in-depth interviews with pregnant and lactating women, focus group discussions with caregivers, and key informant interviews with health workers and local stakeholders, alongside non-participant observations. Interviews will take place during and shortly after the heat season to capture both real-time and reflective experiences. Using purposive sampling, we will recruit 20-25 women per site, along with caregivers and stakeholders, primarily from the HiP-India cohort who have consented to follow-up. Data will be thematically analysed using NVivo, with reporting guided by COREQ standards. The study will generate contextualised insights into women's heat-adaptation practices during pregnancy and lactation across diverse agro-climatic zones, document traditional and emerging coping strategies, and identify structural, social, and institutional barriers shaping adaptation capacity. By centering women's lived experiences, this research will inform the design of culturally appropriate, gender-responsive heat adaptation interventions suitable for low-resource settings. Findings will support both practical community-based solutions and evidence-based advocacy for more inclusive climate adaptation policies at local and national levels. Heat Resilience Among Pregnant and Breastfeeding Women in India  As climate change intensifies across India, extreme heat that threatens pregnant women’s health and their babies’ development. Despite their heightened vulnerability, their specific needs remain largely overlooked in both climate adaptation planning and healthcare systems. Recognising this critical gap, researchers from the Heat in Pregnancy (HiP) consortium have launched the HiP-India project to better understand how women navigate these challenges. The study will take place during the summers of 2025–2026 across three diverse locations — Gurugram (Haryana), Bilaspur (Chhattisgarh), and Puducherry — representing different environmental and cultural contexts within India. The research team will talk directly with pregnant and breastfeeding women to understand their daily experiences and how they adjust to heat. They will also speak with family members, community health workers, and local leaders to gain a better understanding of the support available and the challenges women face in staying safe during hot weather. The findings will show how heat affects maternal health and what kinds of support women need. The main goal is to inform better policies and programs that meet the needs of women during pregnancy and early motherhood by identifying practical, affordable, and locally relevant solutions that build resilience and improve health outcomes.
Breast cancer is one of the major causes of cancer-related illnesses and deaths globally, which calls for the use of advanced technologies in early diagnosis, precise imaging, and effective therapy. Quantum dots (QDs) have become extremely versatile nanomaterials due to their size-dependent optical properties, large surface area, and easily modifiable physicochemical properties; thus, they can be used in a wide range of applications from diagnosis to therapy. Latest changes show that inorganic, carbon-based, and graphene-derived QDs can be made more biocompatible, controllable in their targeting, and multifunctional by their synthesis and surface functionalization. Great strides have been made in diagnostic applications such as very sensitive electrochemical and optical biosensors, radiolabeled QD probes, and quantum-optimised artificial intelligence-assisted imaging systems, which can detect at femtogram levels, provide high specificity, and are stable in complicated biological matrices. At the same time, therapeutic interventions including QD-mediated drug delivery, photothermal and photodynamic therapy, and nano-immunotherapy have been demonstrated to exhibit strong antitumor effects, inhibition of tumour recurrence and metastasis, immune microenvironment modulation, and decreased systemic toxicity in animal models. Efforts to transition clinical translation further highlight the increasing significance of QD-based platforms. Taken together, these discoveries position QDs as a potential nanotheranostic platform of the next generation with considerable ability to revolutionize breast cancer diagnosis, treatment precision, and patient outcomes, which, however, necessitate solving issues related to long-term safety, production scalability, and regulatory challenges before successful clinical implementation can take place.
Given significant advances in the treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of chronic liver diseases in Bangladesh may be changing. Our aim was to assess the shift in the prevalence of different chronic liver disease etiologies in a tertiary level hospital of Bangladesh over the last 10 years. This was a retrospective observational study conducted in the Department of Hepatology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. It was based on data from the hospital records (2013-2016 and 2017-2022). A total of 4658 patients were included from the hospital registry between 2013 and 2022. The etiologies of chronic liver disease were compared between two time periods: (2013-2016) and (2017-2022) among these patients. A significant decrease in the prevalence of chronic hepatitis B from 51.1% (2013-2016) to 44.4% (2017-2022) (p < 0.001), chronic hepatitis C from 11.3% (2013-2016) to 10.4% (2017-2022) (p = 0.032), and non-B-non-C from 11.7% (2013-2016) to 8.6% (2017-2022) (p < 0.001) was observed. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD/NASH) increased from 1.2% (2013-2016) to 8.1% (2017-2022) (p < 0.001); anti-HBc (total) from 3.2% (2013-2016) to 5.1% (2017-2022) (p = 0.001), and autoimmune hepatitis (AIH) from 0.2% (2013-2016) to 0.4% (2017-2022) (p = 0.038) also showed a significant increase. Over the last decade (2013-2022), NAFLD has emerged as a rapidly increasing cause of chronic liver disease in Bangladesh, whereas viral etiologies and AIH show a declining trend. Policy makers, clinicians, and stakeholders should take attention to recognize the situation and act properly.
It is always expected that tunneling coupling splits the energy of the eigenstates in proportion to its magnitude. This is also true for bound states in the continuum (BICs) in the waveguide strongly coupled to a Fabry-Pérot resonator. However, in the case of weak coupling, giant enhancement of the splitting takes place. Within the tight-binding model, we show that, in the limit of a weak coupling, the BIC formation conditions take a universal form independent of the particular structure of the periodic perturbations. Moreover, BIC energies become almost uniformly distributed over the energy band of the waveguide in agreement with the Erdős-Turán theorem. Analytical conclusions are supported by numerical calculations of two-dimensional waveguides with finite periodic modulation for both quantum-mechanical and optical cases. The results present a new approach to BIC construction and may pave the way towards quantum design of large-scale integrated systems of giant atoms with spatially distributed coupling to waveguides.
Cognitive behavioral therapy (CBT) is the most effective treatment for binge eating disorder (BED) but is limited by modest efficacy and low reach of in-person delivery. Combining mindfulness training with CBT could enhance efficacy by targeting emotion dysregulation, a key factor in BED that CBT does not adequately target. Digital delivery can enhance the reach of treatment. Accordingly, we developed CBT-based Mindful Courage, a 16-session digital intervention combining CBT and mindfulness training for BED. The aim of this study is to conduct a pilot randomized controlled trial to evaluate the feasibility (intervention and assessment completion) and acceptability (usability, overall satisfaction, engagement, visual appeal of content, understandability of program content, desire to continue the program, perceived skill acquisition, perceived confidence in implementing skills, and perceived helpfulness) of CBT-based Mindful Courage. We will also evaluate changes in outcomes (binge eating frequency, eating disorder symptoms, clinical impairment, and depression symptoms) and mechanisms (emotion dysregulation, dietary overrestriction, and trait mindfulness). This is a parallel-group, single-blinded, randomized controlled trial with a 1:1 allocation ratio. It will be conducted from November 2025 to November 2026, with study assessments at baseline, midtreatment, end-of-treatment, and 2-month follow-up. We will recruit a volunteer sample of adults with BED (N=40) aged 18 to 75 years via online advertisements. Exclusion criteria include a BMI <18.5, current anorexia or bulimia nervosa, and current treatment for BED or weight loss. Participants will be randomly allocated to an active control that includes coached self-monitoring (self-monitoring of food intake in Recovery Record and coaching calls by a research assistant) or to CBT-based Mindful Courage+coached self-monitoring. Both conditions will have a duration of 18 weeks. All study sessions will take place over Zoom. The study was funded in April 2023. Data collection began in November 2025, and we anticipate recruitment to be completed by November 2026. Results are expected to be analyzed by May 2027 and published by May 2028. This will be an important first step in creating a scalable and efficacious treatment for BED. ClinicalTrials.gov NCT07212673; https://clinicaltrials.gov/study/NCT07212673. DERR1-10.2196/91761.
Post-traumatic stress disorder (PTSD) is a common psychiatric condition, with a global prevalence of 3.9% and a lifetime prevalence of 7.4% in the Netherlands. Although numerous evidence-based treatments are available, their use varies considerably. Understanding patient perspectives and experiences in the decision-making process when choosing a specific treatment is crucial for improving the quality of care. This study aimed to explore the decision-making process from the perspective of patients with PTSD, focusing on their considerations and experiences when choosing a specific psychotherapeutic treatment. In this qualitative study, twelve semi-structured interviews were conducted with patients with PTSD (aged 21-55 years) receiving care at a mental health organisation in the east of the Netherlands. Data were analysed using reflexive thematic analysis, informed by grounded theory-inspired analytic techniques. Analysis was iterative and inductive, focusing on the identification and interpretation of patterns of meaning across patients' accounts. Five themes were identified, connected through an overarching interpretive concept of patient-attunement: (1) the role of treatment characteristics (2), the role of therapeutic factors (3), the role of treatment duration and intensity (4), the role of significant others, and (5) the role of information about trauma-focused treatment. Patients emphasised the importance of personalised information and support from clinicians and significant others. Ongoing responsiveness within the therapeutic relationship, including trust and collaboration, was central to experiencing the decision-making process as supportive and meaningful. For patients with post-traumatic stress disorder, multiple factors play a role in choosing a psychotherapeutic trauma-focused treatment. This study shows that continued attunement to patients' diverse needs is central to the decision-making process. Such attunement may take various forms, including attention to the therapeutic relationship, discussion of treatment characteristics and frequency, and responsiveness to patients' preferences regarding information provision. Involving patients' support systems may further support decision-making. Together, these findings suggest that clinicians should remain attentive to patients' needs at multiple points during the pre-treatment phase. Approaches such as shared decision-making may help facilitate this attunement. Not applicable.
Optically active networks show feature-rich emission that depends on the fine details of their geometry and find diverse applications in random lasers, sensing devices, and photonics processors. In these and other systems, a thorough and predictive characterization of how the network geometry correlates with the resulting emission spectrum would be highly important; however, such an outright description is still lacking. In this work, we take a step toward filling this gap by using the well-known Steady-state Ab initio Laser Theory equations to carry out an extensive set of statistical analyses and establish connections between the random network geometry and their ultimate emission spectrum. Our results show that edge crowding (abundance of short edges in the network) is key to tuning the uniformity of the modal intensity distribution of the emission spectrum. A statistical framework for the comprehensive understanding of the network statistical properties is highly significant to establish precise design rules for network-based photonic devices and intelligent systems.
Patients with neurodegenerative diseases are often assessed using rating scales containing a number of items, where each item is scored based on an ordinal scale of 0 to K (0 indicating normal function and K indicating severe impairment). The total score, calculated as the total sum of the items, is commonly used for subsequent analysis due to its simplicity. However, the total score is treated as a continuous value and does not respect the ordinal nature of the item-level data. In addition, the total score may lead to information loss as neurodegenerative diseases are multi-faceted, and using a single numeric value may not effectively represent the disease progression. In this article, we propose a convolutional neural network (CNN) designed to take longitudinal ordinal items as input and predict patients' future survival trajectories. We demonstrate that using the item-level data improves the predictive performance in comparison to traditional joint models using the total score. These advantages are shown through both a simulation study and real data application to a Parkinson's disease study.
A traditional view of selective attention distinguishes between goal-directed and stimulus-driven mechanisms of attentional control. More recently, a large (and growing) body of research has identified a third class of control system-termed selection history-wherein attentional prioritisation is shaped by our prior experience with stimuli, independently of our goals and the physical salience of those stimuli. This article reviews work within this selection history literature demonstrating that prioritisation is rapidly and automatically modulated by learning about the rewards associated with stimuli, and argues for a framework that distinguishes between history-driven processes implementing attentional exploitation (the drive to leverage reliable information) and attentional exploration (the drive to resolve uncertainty, with the aim of validating potential new sources of information). Findings such as these highlight a fundamental and intricate interaction between learning and attention, wherein our prior experience shapes the way in which we extract information from our environment - with potential consequences for understanding the subsequent decisions that we make and choices that we take.
When outbreaks of emerging and reemerging zoonotic diseases are discussed, little attention is paid to differential gender impacts, or to gender involvement and roles in different settings during the outbreak. Gender roles shape how individuals' interactions with animals, wildlife, other people and the environment, which influences exposure to zoonotic pathogens. For example, in some rural communities, men may face risks of exposure to emerging pathogens during hunting whilst women who primarily take care of domestic animals may face prolonged exposure to other zoonotic diseases. In some settings, women (and men) lack access to health protection, education or communication with health officials (medical doctors or veterinarians). In some cultures, women are not allowed to speak directly with male service providers, further limiting their access to critical information and services. One Health is a holistic, inclusive approach which should be incorporating a gender lens when considering zoonoses. This includes thinking about the need to create appropriate gender sensitive policies that address disparities in surveillance, response, prevention, detection, and control of the disease (or health issue) being addressed. In this paper, we highlight these issues through several case studies that demonstrate the importance of including gender in zoonotic disease response and, ideally, when implementing prevention measures.
Biofilm-based microalgal cultivation systems represent a different cultivation technology from suspended algal culturing. Unlike traditional suspended cultures, biofilm systems can offer higher biomass concentrations, simplified harvesting, and great potential for reduced energy consumption. Despite these advantages, challenges such as biofilm detachment, fouling, and scalability exist. These challenges must be addressed before large-scale biofilm cultivation can take place. Integrating biofilm-based systems into circular economy models presents an opportunity for resource recovery and climate change mitigation. This chapter explores the fundamentals of biofilm formation, including mechanisms of adhesion, biofilm structure, and important factors influencing growth dynamics. It provides a broad analysis of reactor designs, substrate materials, and operational parameters optimized for diverse applications.
Genetic mosaicism refers to the presence of two or more genetically distinct cell populations derived from a single zygote, resulting from post-zygotic genetic or epigenetic variation. This phenomenon contributes to diverse clinical presentations across a broad range of disorders and holds significant implications for diagnosis, inheritance risk, and clinical management. This article provides an overview of mosaicism from a clinical perspective, emphasizing its relevance for nurse practitioners. Two types of mosaicism are described with representative conditions: chromosomal mosaicism by trisomy 21 and germline mosaicism illustrated by Duchenne muscular dystrophy. Each clinical case demonstrates how the timing, location, and nature of mosaic variants influence phenotype, recurrence risk, and detection. Clinical pearls are included for each case emphasizing important take-aways for practice. Understanding these mechanisms is essential for interpretation of genetic testing, risk assessment, and counseling and education of affected individuals and their families.
Parental factors are known determinants of internet gaming disorder (IGD) among adolescents. However, the associations between gaming-specific parental factors (eg, parental gaming frequency and parental invitations for cogaming) and IGD have been less investigated, and relevant longitudinal evidence is lacking to inform effective IGD interventions. This study aimed to investigate (1) the prevalence of IGD conversion (from a noncase at baseline to a case at follow-up) and (2) the prospective associations between two parental gaming behaviors and IGD conversion as well as their mediation mechanisms via parental supportive attitude toward adolescents' gaming behaviors and behavioral intention of increasing gaming time. A 12-month prospective longitudinal study, with the baseline survey in December 2018 (T1) and the follow-up survey in December 2019 (T2), was conducted among students from 6 convenience-selection junior middle schools in Chengdu and Guangzhou, China. All grade 7 and 8 students of these schools were invited for participation; students self-administered the structured questionnaire on paper and pencil, in classroom settings, and in the absence of schoolteachers. The 9-item DSM-5 Internet Gaming Disorder Symptoms Checklist was used to assess IGD (Cronbach α=0.73). Those with IGD at T1 were excluded, and the final sample size was 2172 (mean age 12.56, SD 0.02, 95% CI 12.52-12.60 years; n=1102, 50.7%, 95% CI 48.7%-52.8% female). The prevalence of IGD conversion was 5.2% (113/2172; 95% CI 4.4%-6.1%). Adjusted for background factors and respective mediator and outcome scores at T1, two path analysis models showed satisfactory model fit indices (ie, root mean square error approximation=0.02 and 0.03, comparative fit index=0.97 for both models, and standardized root mean square residual=0.02 for both models). The prospective associations between perceived parental gaming frequency and perceived parental invitations for cogaming and IGD conversion were significantly and fully mediated by the 1-mediator indirect path via parental supportive attitude (β=0.02, 95% CI 0.01-0.04 and β=0.02, 95% CI 0.01-0.04) and the 2-mediator indirect path first via parental supportive attitude and then via behavioral intention of increasing gaming time (β=0.006, 95% CI 0.002-0.009 and β=0.005, 95% CI 0.001-0.009) but not the 1-mediator indirect path via the behavioral intention (β=0.01, 95% CI -0.01 to 0.03 and β=0.01, 95% CI -0.01 to 0.03), respectively. This longitudinal study revealed the prospective associations between 2 parental gaming behaviors and adolescent IGD conversion, as well as the mediation mechanisms, addressing inconsistencies in previous cross-sectional studies and filling in the knowledge gap in longitudinal studies that overlooked parental gaming behaviors. It suggests that parental gaming behaviors may form important family environments shaping adolescents' perceptions and behaviors related to internet gaming. Family-based prevention and intervention programs on IGD conversion may hence take into account these findings.
Two isoforms of the 90-kDa heat shock protein (Hsp90), stress-inducible Hsp90α and constitutively expressed Hsp90β, function in mammalian cells as molecular chaperones that promote the folding of specific client proteins involved in essential cellular processes and regulatory pathways. A number of Hsp90 client proteins take part in cancer progression, and the inhibition of Hsp90 induces the degradation of oncogenic client proteins and cancer cell death. Hsp90 inhibitors specific for individual Hsp90 isoforms have a significant potential for the development of anticancer therapeutics due to reduced toxicity. Cells with knocked-out genes encoding Hsp90 isoforms represent excellent cellular models to investigate the rearrangement of the cell chaperone machinery in response to the suppression/loss of the Hsp90 isoforms. Recently, we have shown that the knockout of the HSP90AA1 gene encoding Hsp90α in human fibrosarcoma HT1080 cells does not affect basic cellular processes in normal and stressful conditions, which suggests an adaptation of the cell chaperone machinery to the loss of Hsp90α. Here, we demonstrated that the lack of Hsp90α in HT1080 cells leads to an up-regulation of the constitutively expressed Hsp90β and several important Hsp90 co-chaperones (Aha1, Hop, and others). The expression of the major chaperones of the Hsp70 machinery (Hsp70-1, Hsp70-2, Hsc70) was also significantly induced. The components of the prefoldin-chaperonin folding arm and PFDL, R2TP, and R2SP complexes, as well as the major mitochondrial chaperones, were also largely up-regulated in Hsp90α-KO cells, while the expression of ER-resident chaperones/co-chaperones was either repressed or did not change. We demonstrated here for the first time an adaptation of the cell chaperone machinery to the loss of the Hsp90α chaperone, which may be important for understanding the molecular mechanisms of action of Hsp90α-specific inhibitors and elaborating new therapy strategies in combating cancer, including the combination of Hsp90α-targeted therapy.
The capture of patient baseline characteristics in randomized controlled trials (RCTs) is essential for assessing external validity and for exploring treatment effect heterogeneity. Yet, the capture of such information is highly inconsistent across trials with limited harmonization efforts to date. The International Consortium for Health Outcomes Measurement (ICHOM) has issued expert recommendations for baseline characteristics to capture in clinical practice, as part of Sets of Patient-Centered Outcome Measures ("Sets"). We reviewed which characteristics were recommended across different conditions, and how they were to be measured. We systematically retrieved and included all ICHOM Sets that were published in peer-reviewed journals and issued measurement recommendations for adult populations. For each Set, we extracted measurement recommendations pertaining to patients' individual baseline characteristics ("case-mix factors") from the Set's data collection reference guide. We used inductive thematic coding to harmonize variable names, and group them into thematic factors and domains. Two reviewers independently coded factors and resolved disagreements. We also extracted the recommended approach to measuring each factor. We identified 32 eligible ICHOM Sets covering a range of conditions that make important contributions to the global disease burden (e.g. coronary artery disease, diabetes, depression). These Sets identified 616 original baseline variables for measurement, which we mapped onto 89 thematic factors. We identified factors that were repeatedly recommended across conditions, with a focus on sixteen factors appearing in at least 15% of Sets. These included demographics such as age, sex, gender, race/ethnicity; clinical factors such as comorbidities and disease onset; and psychosocial factors such as education, tobacco and alcohol consumption, employment, relationship status, and physical activity. For most of these factors, ICHOM recommended brief assessments via one or two questions. Only for comorbidities and physical activity did the recommended approaches include multi-item instruments, namely the Self-administered Comorbidity Questionnaire and the International Physical Activity Questionnaire Short Form, respectively. Only six factors were recommended in more than 50% of Sets. There is scope to harmonize baseline measurement in RCTs both within conditions, drawing on clinical and physiological patient characteristics with condition-specific relevance, and across conditions, based on recurrent demographic and psychosocial factors. Clinical trials need to collect clear and consistent information about the people who take part. This information is essential for understanding who the trial findings apply to and whether different groups of people may respond differently to a treatment. However, this type of information is currently collected in very inconsistent and incomplete ways across trials. In this study, we examined recommendations for patient characteristics to capture that have been developed by expert groups convened by the International Consortium for Health Outcomes Measurement (ICHOM). Although these expert recommendations were designed for measurement in everyday clinical settings rather than research studies, they can potentially inform future efforts to identify similar recommendations specifically for research studies. We reviewed 32 sets of ICHOM measurement recommendations that covered a range of different health conditions. Across these Sets, we found 616 individual baseline variables, which we grouped into 89 thematic factors. Many of these factors were specific to particular diseases, for example clinical measurements or the clinical history of a patient's condition. However, we also identified some demographic and psychosocial factors that were recommended repeatedly for measurement in the context of different conditions. Sixteen such factors were found in at least 15% of Sets, including, for example, age, sex and gender, race and ethnicity, co-occurring health problems, when the disease began, education level, smoking and alcohol use, employment and relationship status, living situation, and physical activity. Most of this information can be obtained from patients using only one or two questions. These findings suggest that it may be possible to develop guidance on what patient information to collect in clinical trials and how, both in terms of information that is relevant for specific conditions and information that has general relevance across diseases. If differences in measurement approaches could be reduced, this would make it easier to interpret, compare, and combine research findings, and could improve our understanding of which treatments work best for which groups of patients.