Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells.

Selective targeting of cancer stem cells (CSCs) offers promise for a new generation of therapeutics. However, assays for both human CSCs and normal stem cells that are amenable to robust biological screens are limited. Using a discovery platform that reveals differences between neoplastic and normal human pluripotent stem cells (hPSC), we identify small molecules from libraries of known compounds that induce differentiation to overcome neoplastic self-renewal. Surprisingly, thioridazine, an antipsychotic drug, selectively targets the neoplastic cells, and impairs human somatic CSCs capable of in vivo leukemic disease initiation while having no effect on normal blood SCs. The drug antagonizes dopamine receptors that are expressed on CSCs and on breast cancer cells as well. These results suggest that dopamine receptors may serve as a biomarker for diverse malignancies, demonstrate the utility of using neoplastic hPSCs for identifying CSC-targeting drugs, and provide support for the use of differentiation as a therapeutic strategy.

A spatial examination of alcohol availability and the level of disadvantage of schools in Ireland.

BACKGROUND: The availability of alcohol is a major factor in underage drinking and according to the alcohol harm paradox, those living in more deprived communities are more susceptible to the negative consequences of alcohol use, despite drinking the same or less than those from more affluent areas. Alcohol availability within the vicinity of the home or school normalises alcohol for schoolchildren. For the first time in the Republic of Ireland, this study examines the number of premises licensed to sell alcohol within 300 m of all schools in Ireland and differences in this number between disadvantaged and non-disadvantaged schools. METHODS: Using publicly available data from the Department of Education and Revenue, the addresses of all schools (n = 3,958) and all premises with at least one liquor licence (n = 14,840) were geocoded and analysed using the Geographic Information System software, Quantum GIS (QGIS). Schools were identified by their disadvantaged classification using the HP Pobal Deprivation Index and the number of liquor licences within 300 m of each school type was examined. To test for significant differences between schools' level of disadvantage, a combination of Mann-Whitney U tests, Kruskal-Wallis tests and Dunn-Bonferroni tests were used. RESULTS: There was a mean of two licenced premises within 300 m of all schools in Ireland, but when disadvantaged schools were compared to non-disadvantaged schools, there was a significantly higher number of licenced premises around disadvantaged schools (p < .001). Primary schools are further classified according to their level of disadvantage and the results indicated that those schools classified as the most disadvantaged had a significantly greater number of liquor licences within 300 meters (p < .001). There was no significant difference in density of licenced premises when comparing disadvantaged secondary schools with non-disadvantaged secondary schools (p = .705). CONCLUSION: Ireland is considering increasing alcohol availability through the Sale of Alcohol Bill, 2022. However, this analysis indicates already problematic numbers of licenced premises within close proximity of schools in Ireland. It is essential that the harms associated with alcohol availability are considered, especially for those living and attending school in disadvantaged communities, where higher numbers of licenced premises were identified.

A health data led approach for assessing potential health benefits of green and blue spaces: Lessons from an Irish case study.

Research producing evidence-based information on the health benefits of green and blue spaces often has within its design, the potential for inherent or implicit bias which can unconsciously orient the outcomes of such studies towards preconceived hypothesis. Many studies are situated in proximity to specific or generic green and blue spaces (hence, constituting a green or blue space led approach), others are conducted due to availability of green and blue space data (hence, applying a green or blue space data led approach), while other studies are shaped by particular interests in the association of particular health conditions with presence of, or engagements with green or blue spaces (hence, adopting a health or health status led approach). In order to tackle this bias and develop a more objective research design for studying associations between human health outcomes and green and blue spaces, this paper discussed the features of a methodological framework suitable for that purpose after an initial, year-long, exploratory Irish study. The innovative approach explored by this study (i.e., the health-data led approach) first identifies sample sites with good and poor health outcomes from available health data (using data clustering techniques) before examining the potential role of the presence of, or engagement with green and blue spaces in creating such health outcomes. By doing so, we argue that some of the bias associated with the other three listed methods can be reduced and even eliminated. Finally, we infer that the principles and paradigm adopted by the health data led approach can be applicable and effective in analyzing other sustainability problems beyond associations between human health outcomes and green and blue spaces (e.g., health, energy, food, income, environment and climate inequality and justice etc.). The possibility of this is also discussed within this paper.

Perceptions of Change in the Natural Environment produced by the First Wave of the COVID-19 Pandemic across Three European countries. Results from the GreenCOVID study.

Although different studies have evaluated the positive impacts of the COVID-19 pandemic and lockdown measures on reducing noise pollution and traffic levels and improving air quality, how populations have perceived such changes in the natural environment has not been adequately evaluated. The present study provides a more in-depth exploration of human population perception of enhanced natural exposure (to animal life and nature sounds) and reduced harmful exposure (by improved air quality and reduced traffic volume) as a result of the COVID-19 pandemic lockdown. The data is drawn from 3,109 unselected adults who participated in the GreenCOVID survey from April to July 2020 in England, Ireland, and Spain. The findings suggest that the positive impacts to the natural environment as a result of the lockdown have been better received by the population in Spain and Ireland, in comparison to England. Participants who resided in urban areas had better perceived improvements in nature sounds, air quality, and traffic volume compared to those in rural areas. Older populations and those with lower smoking and alcohol consumption were found to perceive this improvement the most. Furthermore, the greater perception of improvements in environmental elements was also associated with better self-perceived health and improved wellbeing. In the binary logistic regression, living in Ireland or Spain, urban areas, female gender, older age, and good overall wellbeing were associated with a greater perception of improvements in the natural environment, while the factors most associated with a greater perception of reduced harmful exposure were living in Spain, had a good self-perceived health status and older age.

CD56bright natural killer regulatory cells in filgrastim primed donor blood or marrow products regulate chronic graft-versus-host disease: the Canadian Blood and Marrow Transplant Group randomized 0601 study results.

Randomized trials have conclusively shown higher rates of chronic graft-versus-host disease with filgrastim-stimulated apheresis peripheral blood as a donor source than unstimulated bone marrow. The Canadian Blood and Marrow Transplant Group conducted a phase 3 study of adults who received either filgrastim-stimulated apheresis peripheral blood or filgrastim-stimulated bone marrow from human leukocyte antigen-identical sibling donors. Because all donors received the identical filgrastim dosing schedule, this study allowed for a controlled evaluation of the impact of stem cell source on development of chronic graft-versus-host disease. One hundred and twenty-one evaluable filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow patient donor products were immunologically characterized by flow cytometry and tested for their association with acute and chronic graft-versus-host disease within 2 years of transplantation. The immune populations evaluated included, regulatory T cells, central memory and effector T cells, interferon γ positive producing T cells, invariate natural killer T cells, regulatory natural killer cells, dendritic cell populations, macrophages, and activated B cells and memory B cells. When both filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow were grouped together, a higher chronic graft-versus-host disease frequency was associated with lower proportions of CD56bright natural killer regulatory cells and interferon γ-producing T helper cells in the donor product. Lower CD56bright natural killer regulatory cells displayed differential impacts on the development of extensive chronic graft-versus-host disease between filgrastim-stimulated apheresis peripheral blood and filgrastim-stimulated bone marrow. In summary, while controlling for the potential impact of filgrastim on marrow, our studies demonstrated that CD56bright natural killer regulatory cells had a much stronger impact on filgrastim-stimulated apheresis peripheral blood than on filgrastim-stimulated bone marrow. This supports the conclusion that a lower proportion of CD56bright natural killer regulatory cells results in the high rate of chronic graft-versus-host disease seen in filgrastim-stimulated apheresis peripheral blood. clinicaltrials.gov Identifier: 00438958.

The relationship of CD34+ dosage and platelet recovery following high dose chemotherapy and autologous CD34+ reinfusion in multiple myeloma.

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for multiple myeloma (MM), yet the impact of transplanted CD34+ cell dose remains unresolved, especially in patients over the age of 65 years. Data was collected from 207 consecutive ASCT patients to determine the relationship between CD34+ infusion count and short-term and long-term platelet recovery. For MM patients under the age of 65 years (n=155), CD34+ dosage correlates with time to platelet engraftment (p<0.001) and platelet count at 30 days (p=0.003), but not with long-term platelet counts at 180 or 360 days from the CD34+ reinfusion. For MM patients aged 65 years or older (n=46), CD34+ dosage did not correlate with time to platelet engraftment, but did correlate with both short-term and long-term platelet counts at 30 (p<0.001), 180 (p=0.021), and 360 days (p=0.005). Exploratory regression analysis was done to explore platelet stability following the current minimum CD34+ dosage reinfusion. For MM patients under the age of 65 years, the minimum standard CD34+ dosage of 2×106cells/kg was sufficient for a timing to platelet engraftment of <21 days and short-term platelets count ≥150×109/L at 30 days. Alternatively, for MM patients aged 65 years or older, the CD34+ dosage of 2×106cells/kg was insufficient for platelet counts ≥150×109/L at 30 and only marginally attainable at 360 days suggesting that in elderly MM patients a higher CD34+ dosage may be required for platelet recovery and possibly long-term platelet stability.

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial.

BACKGROUND: Pretreatment with anti-thymocyte globulin (ATG) decreases the occurrence of chronic graft-versus-host disease (CGVHD) after haemopoietic cell transplantation from an unrelated donor, but evidence of patient benefit is absent. We did a study to test whether ATG provides patient benefit, particularly in reducing the need for long-term immunosuppressive treatment after transplantation. METHODS: We did a phase 3, multicentre, open-label, randomised controlled trial at ten transplant centres in Canada and one in Australia. Eligible patients were aged 16 to 70 years with any haematological malignancy and a Karnofsky score of at least 60 receiving either myeloablative or non-myeloablative (or reduced intensity) conditioning preparative regimens before haemopoietic cell transplantation from an unrelated donor. We allocated patients first by simple randomisation (1:1), then by a minimisation method, to either pretransplantation rabbit ATG plus standard GVHD prophylaxis (ATG group) or standard GVHD prophylaxis alone (no ATG group). We gave a total dose of ATG of 4·5 mg/kg intravenously over 3 days (0·5 mg/kg 2 days before transplantation, 2·0 mg/kg 1 day before, and 2·0 mg/kg 1 day after). The primary endpoint was freedom from all systemic immunosuppressive drugs without resumption up to 12 months after transplantation. Analysis was based on a modified intention-to-treat method. This trial was registered at ISRCTN, number 29899028. FINDINGS: Between June 9, 2010, and July 8, 2013, we recruited and assigned 203 eligible patients to treatment (101 to ATG and 102 to no ATG). 37 (37%) of 99 patients who received ATG were free from immunosuppressive treatment at 12 months compared with 16 (16%) of 97 who received no ATG (adjusted odds ratio 4·25 [95% CI 1·87-9·67]; p=0·00060. The occurrence of serious adverse events (Common Terminology Criteria grades 4 or 5) did not differ between the treatment groups (34 [34%] of 99 patients in the ATG group vs 41 [42%] of 97 in the no ATG group). Epstein-Barr virus reactivation was substantially more common in patients who received ATG (20 [one of whom died-the only death due to an adverse event]) versus those who did not receive ATG (two [no deaths]). No deaths were attributable to ATG. INTERPRETATION: ATG should be added to myeloblative and non-myeloblative preparative regimens for haemopoietic cell transplantation when using unrelated donors. The benefits of decreases in steroid use are clinically significant. Epstein-Barr virus reactivation is increased, but is manageable by prospective monitoring and the use of rituximab. Future trials could determine whether the doses of ATG used in this trial are optimum, and could also provide additional evidence of a low relapse rate after non-myeloablative regimens. FUNDING: The Canadian Institutes of Health Research and Sanofi.

Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors From AML Patients That Are Devoid of Patient-Specific Genomic Aberrations.

Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient-specific leukemic aberrations from AML patients must first be evaluated. Here, we report the generation of human AML patient-specific hematopoietic progenitors that are capable of normal in vitro differentiation to myeloid lineages and are devoid of leukemia-associated aberration found in matched patient bone marrow. Skin fibroblasts were obtained from AML patients whose leukemic cells possessed a distinct, leukemia-associated aberration, and used to create AML patient-specific induced pluripotent stem cells (iPSCs). Through hematopoietic differentiation of AML patient iPSCs, coupled with cytogenetic interrogation, we reveal that AML patient-specific HPCs possess normal progenitor capacity and are devoid of leukemia-associated mutations. Importantly, in rare patient skin samples that give rise to mosaic fibroblast cultures that continue to carry leukemia-associated mutations; healthy hematopoietic progenitors can also be generated via reprogramming selection. Our findings provide the proof of principle that cellular reprogramming can be applied on a personalized basis to generate healthy HPCs from AML patients, and should further motivate advances toward creating transplantable hematopoietic stem cells for autologous AML therapy.

Favorable outcomes from allogeneic and autologous stem cell transplantation for patients with transformed nonfollicular indolent lymphoma.

The role of allogeneic (allo-) and autologous stem cell transplantation (auto-SCT) in the management of patients with transformed indolent nonfollicular non-Hodgkin lymphoma is unknown. This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B cell nonfollicular non-Hodgkin lymphoma and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with allo-SCT or auto-SCT between 1996 and 2013. All patients received myeloablative conditioning regimens. Outcomes were compared with a cohort of 246 patients with transformed follicular lymphoma who also underwent allo-SCT (n = 47) or auto-SCT (n = 199) across the same institutions and time frame. Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent allo-SCT, whereas 33 (65%) underwent auto-SCT. The 3-year overall survival rate after transplantation was 67% (allo-SCT 54%, auto-SCT 74%), and 3-year progression-free survival rate was 49% (allo-SCT 40%, auto-SCT 54%). The 3-year nonrelapse mortality rate was 14% (allo-SCT 15%, auto-SCT 7%). Transplant-related mortality at 100 days was 17% for allo-SCT and 0% for auto-SCT. Adjusted for type of stem cell transplantation, 3-year overall survival, progression-free survival, and nonrelapse mortality rates were similar to those of patients with transformed follicular lymphoma receiving allo-SCT and auto-SCT (P = .38, P = .69, and P = .54, respectively). Allo-SCT and auto-SCT may be reasonable treatments for selected patients with transformed nonfollicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with auto-SCT.

Identification of a Patient Suitable for CAR-T Cell Therapy in the Outpatient Setting: A Vodcast and Case Example.

Chimeric antigen receptor T cell (CAR-T) therapies targeting the CD19 antigen have been associated with high and durable response rates in patients with diffuse large B cell lymphoma (DLBCL). CAR-T cell therapies are commonly administered in the inpatient setting due to the average onset of cytokine release syndrome within the first 3 days post infusion, but there has been growing interest in delivering CAR-T cell therapies in the outpatient setting to overcome frequent hospital bed shortages and the high cost of inpatient care. Although this approach could improve access whilst catering to patient preference, it requires a multidisciplinary approach as well as careful patient selection. Herein, Dr. Foley and Dr. Kuruvilla discuss the case of a patient presenting with the ideal profile for CAR-T cell therapy referral whilst also determining the key attributes for eligibility from a clinician's perspective. Solutions for successful outpatient management include proper education, caregiver support, and early referral to ensure a timely infusion. In conclusion, outpatient administration of CAR-T cell therapy in patients with DLBCLs should be assessed on a case-by-case basis.A vodcast feature is available for this article.

"When we were allowed to go back the freedom, the vista, the delight It was just magic": Disruption and adaptation among people ageing-in-place in Ireland during COVID-19.

COVID-19 person-place disruptions may dislocate enabling resources and affect the short- and long-term wellbeing of individuals ageing-in-place. However, outcomes may vary according to individuals' personal experiences and capabilities to put in place adaptive strategies. Underpinned by the Conservation of Resources (COR) Theory, this study aimed to identify shifts in older people's relationships to place during the pandemic and to gain a deeper understanding of their adaptive strategies. We analysed data collected between April-May and October-November 2021 from the [Details omitted for double-blind reviewing], a qualitative investigation of community-dwellers based in Ireland and aged 65 years or over. Participants (n = 57) completed written submissions, narrative interviews and/or go-along interviews detailing their experiences during the pandemic. The mean age of participants was 74.9 years, 53% were female, 46% lived alone, and 86% lived in areas with high urban influence. Our framework analysis identified three thematic categories: 1) Characterization of individuals experiencing flow or disruption of place-resources; 2) Effects of place-resource disruptions; and 3) Adaptive strategies to manage disruption. Findings suggest that during the pandemic individuals ageing-in-place experienced trajectories of resistant flow, resilient flow, chronic disruption, or delayed disruption of place-resources, Participants' health and wellbeing was influenced in diverse ways by the threat of- and actual loss of material, social and affective resources. To compensate for disruptions, participants developed multiple adaptive strategies that highlight older people's potential to transform themselves, others, and their environments during times of adversity. These findings showcase the processes by which health enabling places may be maintained and generated, and present areas of opportunity for public health interventions seeking to support ageing populations during public health emergencies and beyond.

Treatment Pattern, Healthcare Resource Utilization and Symptom Burden Among Patients with Triple Class Exposed Multiple Myeloma: A Population-Based Cohort Study.

PURPOSE: This study aims to describe the treatment patterns, outcomes, health care utilization and symptom burden of triple class exposed (TCE) relapsed/refractory patents with multiple myeloma (MM) receiving a subsequent line of treatment (LOT). METHODS: This is a retrospective observational cohort study using administrative databases in Ontario, Canada. Outcomes were captured for TCE patients receiving a subsequent LOT and included: treatment regimen details, time to next treatment (TTNT), overall survival (OS), health care utilization, palliative care referral, and patient reported symptoms. RESULTS: Of the 16,777 patients diagnosed with MM between 2007-2021 in Ontario, 1358 (8%) patients were classified as TCE. Among the TCE MM patients, 489 (36%) received a subsequent LOT. The two most commonly administered therapies post TCE were carfilzomib/dexamethasone (n = 111, 22%) and pomalidomide/dexamethasone(n = 95, 19%). Median TTNT was 1.7 months (95%CI 1.2-2.4 months) and median OS 12.8 months (95%CI 10.8-16.5). Healthcare utilization was high with 276 (56%) of patients evaluated in an emergency department (ED) or admitted to hospital. There was high symptom burden as reported by patients with moderate-severe impairment in well-being, fatigue, pain and drowsiness noted in greater than 25% of the cohort. Palliative care referrals rates were low with only 10% (n = 48) patients referred to palliative care. Among the patients that died during study follow up, the majority died in hospital (n = 147,44%). CONCLUSION: Our study reports one of the largest series of real-world TCE patients published and demonstrates the poor outcomes of TCE patients receiving a subsequent LOT.

Identification of cells of leukemic stem cell origin with non-canonical regenerative properties.

Despite most acute myeloid leukemia (AML) patients entering remission following chemotherapy, outcomes remain poor due to surviving leukemic cells that contribute to relapse. The nature of these enduring cells is poorly understood. Here, through temporal single-cell transcriptomic characterization of AML hierarchical regeneration in response to chemotherapy, we reveal a cell population: AML regeneration enriched cells (RECs). RECs are defined by CD74/CD68 expression, and although derived from leukemic stem cells (LSCs), are devoid of stem/progenitor capacity. Based on REC in situ proximity to CD34-expressing cells identified using spatial transcriptomics on AML patient bone marrow samples, RECs demonstrate the ability to augment or reduce leukemic regeneration in vivo based on transfusion or depletion, respectively. Furthermore, RECs are prognostic for patient survival as well as predictive of treatment failure in AML cohorts. Our study reveals RECs as a previously unknown functional catalyst of LSC-driven regeneration contributing to the non-canonical framework of AML regeneration.

Cellular MRI as a suitable, sensitive non-invasive modality for correlating in vivo migratory efficiencies of different dendritic cell populations with subsequent immunological outcomes.

The clinical application of dendritic cells (DC) as adjuvants in immunotherapies such as the cell-based cancer vaccine continues to gain interest. The overall efficacy of this emerging immunotherapy, however, remains low. Studies suggest the stage of maturation and activation of ex vivo-prepared DC immediately prior to patient administration is critical to subsequent DC migration in vivo, which ultimately affects overall vaccine efficacy. While it is possible to generate mature and activated DC ex vivo using various stimulatory cocktails, in the case of cancer patients, the qualitative and quantitative assessment of which DC stimulatory cocktail works most effectively to enhance subsequent DC migration in vivo is difficult. Thus, a non-invasive imaging modality capable of monitoring the real-time migration of DC in long-term studies is required. In this paper, we address whether cellular magnetic resonance imaging (MRI) is sufficiently sensitive to quantitatively detect differences in the migratory abilities of two different DC preparations: untreated (resting) versus ex vivo matured in a mouse model. In order to distinguish our ex vivo-generated DC of interest from surrounding tissues in magnetic resonance (MR) images, DC were labeled in vitro with the superparamagnetic iron oxide (SPIO) nanoparticle FeREX®. Characterization of DC phenotype and function following addition of a cytokine maturation cocktail and the toll-like receptor ligand CpG, both in the presence and in the absence of SPIO, were also carried out. Conventional histological techniques were used to verify the quantitative data obtained from MR images. This study provides important information relevant to tracking the in vivo migration of ex vivo-prepared and stimulated DC.

Can Views and Contact with Nature at Home Help Combat Anxiety and Depression during the Pandemic? Results of the GreenCOVID study.

BACKGROUND: The COVID-19 pandemic and the lockdown measures have had important consequences on the mental health of the population, although little is known about the role played by nature and its benefits. OBJECTIVES: The present study aims to evaluate the risk of anxiety and depression during the first wave of the COVID-19 pandemic in Spain and to identify the factors most strongly associated with anxiety and depression, including sociodemographic, household characteristics, and access to or contact with natural environment. METHODS: GreenCOVID is an online cross-sectional study promoted by the Health & Territory Research (HTR) of the University of Seville in Spain, Maynooth University in Ireland, and the University of Winchester in the United Kingdom. This study includes only data from Spain which were collected between April 8, 2020 and April 27, 2020. Binary logistic regression was conducted to identify the factors associated with anxiety and depression through the HADS scale. RESULTS: Of the total of 2,464 adults who participated in GreenCOVID Spain, mean age was 38.1 years, 72.6% were female, 58.1% were at risk of anxiety, and 32.3% of depression. In the multivariable logistic regression, the factors associated with risk of anxiety were female: gender, being a student and problems at home. Regarding the risk of depression, the factors most associated were being a student, female gender, problems at home, worse evaluation of views from home and less help from outside views to cope with lockdown. CONCLUSIONS: Our findings show that during COVID-19 pandemic, in addition to sociodemographic factors female gender and being a student, problems at home, lack of natural elements in the home, and worse appreciation of views from home were associated with mental health problems. Thus, housing conditions and access to the natural environment were important for mental health during COVID-19 lockdown.

Socio-ecological determinants of older people's mental health and well-being during COVID-19: A qualitative analysis within the Irish context.

Background: Evidence indicates that older people with biological and social vulnerabilities are at high risk of short- and long-term consequences related to the COVID-19 pandemic. However, studies have also highlighted that the crisis may present opportunities for personal growth if older individuals are met with appropriate resources and support. Objective: The aim of this study was to explore the perceptions of older people regarding how individual, social, and environmental factors have supported or hindered their well-being and health during COVID-19. Methods: We analyzed data collected between April-May and October-November 2021 from the Well-being, Interventions and Support during Epidemics (WISE) study, a qualitative investigation of community-dwellers based in Ireland and aged 65 years or over. Participants (n = 57) completed written submissions, narrative interviews and/or go-along interviews detailing their experiences during the pandemic. Framework analysis was carried out in NVivo 12 to identify determinants, linkages, and explanations within Bronfenbrenner's socio-ecological model. Results: The mean age of participants was 74.9 years, 53% were female, 45% lived alone, and 86% lived in areas with high urban influence. Our findings highlight the heterogeneous effect of COVID-19 across diverse older individuals who held distinct concerns, capabilities, and roles in society before and during the pandemic. Multi-scalar contextual characteristics such as individual's living arrangements, neighborhood social and built environments, as well as social expectations about aging and help seeking, had an influential role in participants' well-being and available supports. We identified mixed views regarding public health restrictions, but a consensus emerged questioning the suitability of one-size-fits-all approaches based on chronological age. Conclusions: Our results suggest that some negative pandemic consequences could have been avoided by increasing collaboration with older people and with the provision of clearer communications. The interdependencies identified between individual characteristics and socio-ecological factors that influenced participants' availability of supports and development of adaptive strategies represent areas of opportunity for the development of age-friendly interventions during and beyond public health crises.

Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia.

We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.