bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effectiveness of Levofloxacin in Prevention of Febrile Episodes in Non-Hodgkin Lymphoma Patients Receiving Rituximab, Cyclophosphamide, Vincristine, Doxorubicin and Prednisolone (R-CHOP)
Authors: Surakijboworn Mutita , Uaprasert Noppachan , Rojnuckarin Ponlapat
Published: December 2024

Background: Febrile neutropenia poses significant risks for morbidity and mortality in non-Hodgkin lymphoma (NHL) patients undergoing R-CHOP chemotherapy. Prophylactic antibacterial use after R-CHOP is controversial, especially when patients receive primary G-CSF prophylaxis, with no established standard recommendation. This study aims to evaluate the effectiveness of levofloxacin in preventing febrile episodes in NHL patients receiving R-CHOP and G-CSF prophylaxis.

Method: A randomized, single-blind, placebo-controlled trial was conducted at King Chulalongkorn Memorial Hospital, enrolling non-Hodgkin lymphoma patients undergoing R-CHOP chemotherapy from January 1, 2023, to June 30, 2024. Patients were randomly assigned to receive either levofloxacin 500 mg once daily or a matching placebo for 7 days, beginning one day after chemotherapy. All patients received primary G-CSF prophylaxis. The primary outcome was the occurrence of febrile episodes within 120 days. Secondary outcomes included rates of septic shock, septic death, all-cause mortality, chemotherapy dose reduction, and the onset of the first febrile episode and composite outcome.

Results: Eighty participants were randomly assigned to two groups, with 40 individuals in each group. Their mean age was 61 years. In the intention-to-treat analysis, febrile episodes occurred in 7.5% and 30% of participants in the levofloxacin and placebo groups, respectively (P = 0.010). Levofloxacin prophylaxis significantly reduced febrile neutropenia (2.5% vs. 20%, P = 0.013), chemotherapy dose reduction (0% vs. 12.5%, P = 0.021), and composite outcome (10% vs. 30%, P = 0.025). The hazard ratio for febrile-free survival with levofloxacin vs. placebo was 0.23 (95% CI 0.06 to 0.8; P = 0.012). No significant differences in infection-related mortality or all-cause mortality were observed between the two groups. Furthermore, no serious adverse effects were documented in either group.

Conclusions: The use of levofloxacin prophylaxis is an effective and well-tolerated strategy in reducing the incidence of febrile episodes, febrile neutropenia, and the need for chemotherapy dose reduction among NHL patients undergoing R-CHOP chemotherapy despite primary G-CSF prophylaxis. Long-term antibiotic resistance monitoring is needed.
Venetoclax Plus Idarubicin and Cytarabine Chemotherapy As First-Line Treatment for Adults with Acute Myeloid Leukaemia
Authors: Zang Shaolei , Ji Min , Zhang Jingru , Lu Fei , Zhang Chunqing , Ye Jingjing , Ji Chunyan
Published: December 2024

Background

3+7(idarubicin/daunorubicin plus cytarabine,IA/DA) has been a standard regimen for first line induction treatment of acute myeloid leukaemia (AML) for half a century. About 60-80% of patients with acute myeloid leukaemia reach complete remission[1], and improved induction regimens are needed. It is in extensive exploration to combine venetocloax with standard cytotoxic drugs for fit AML patients to enhance clinical response. It is proved that venetoclax synergizes with cytarabine and idarubicin to increase antileukemic efficacy in a TP53-dependent manner [2].So in this study we aims to observe the efficacy and safety of lA plus venetoclax (IAV) regimen in newly diagnosed AML patients.

Methods

We enrolled 32 patients aged 18-60 years with previously untreated de-novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Patients had induction treatment with intravenous Idarubicin (12 mg/m² on days 1-3), intravenous cytarabine (100 mg/m² on days 1-7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6-11; IAV regimen). For induction therapy, the length of the treatment was 28-35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events

Findings:

Between October6, 2021 andDecember 31, 2023, 32 patients were enrolled (aged16-60 years; median 46.5years), of which 11/32(34.4%) cases were in favorable risk group, 15/32(46.9%) cases were in intermediate risk group, and 6/32(18.8%) cases were in adverse risk group. 11 (38%) patients were men and 21 (62%) were women, and all were Asian.

(1). Efficacy observation: After one cycle of the lAV regimen, 87.5%(28/32) patients reached cCR, among them 90.6% patients reached MRD negative. With a median follow-up of 9 months, 24/32(75%) patints remain in CR, the median EFS and OS is not reached. The Estimated 12-months EFS is 73.3%(57.7%-93%), and 12-months OS is 86%(73.9%-100%).

(2).Safety observation: During the treatment, some patients experienced adverse reactions and complications including hematologic toxicities, liver and renal dysfunctions, febrile neutropenia. The adverse reactions was tolerated or controlled except one patient died from severe pneumonia after induction chemotherapy. Overall, the regimen was well tolerated in patients with AML at the initial diagnosis.

Conclusion

As an emerging treatment, lAV regimen is effective and safe in newly diagnosed AML patients.
Valoctocogene Roxaparvovec Estimated Long-Term Durability of Treatment Effect: An Extrapolation of the Most Recent Clinical Data
Authors: Santos Sandra , Robinson Tara M. , Trueman David
Published: December 2024

Background: Valoctocogene roxaparvovec is a single administration AAV5-mediated gene therapy that enables endogenous FVIII production to prevent bleeding in people with severe hemophilia A (PwSHA). In the phase 3 GENEr8-1 study, valoctocogene roxaparvovec demonstrated higher probability of being bleed free, improvements in annualized bleeding rates (ABR) and in health-related quality of life (HRQOL) 4 years after infusion when compared to outcomes while on FVIII prophylaxis during the baseline period.

Aims: Estimate the long-term durability of valoctocogene roxaparvovec treatment effect by extrapolating the most recent trial data (GENEr8-1 4-5-year and 270-201 7-year data).

Methods: Durability was analyzed within a time-to-event analysis framework, which is commonly used to extrapolate observed data. The quantity of interest was the rate at which patients experienced loss of response. In alignment with the WFH guidelines and label recommendations, and to reflect the benefit of the treatment as a whole, loss of response was defined in the primary analysis as a clinical overview of an objectively measurable biomarker (FVIII levels <5%), clinical endpoints (≥2 treated bleeds in 6 months) and the return to continuous prophylaxis. The primary analysis used GENEr8-1 data only. Scenario analyses were explored, where other definitions of loss of response were considered, as well as 270-201 7-year data used.

Results: In the primary analysis, the median durability of treatment effect is estimated to range from 11.0-17.0 years. In the scenario where 270-201 data were also used for the extrapolation, median estimated durability is estimated to range from 13.2-20.4 years.

Conclusions: This analysis demonstrates that the observed therapeutic benefit is expected to be sustained beyond the 7 years of follow-up in existing clinical trials, illustrating the full treatment benefit that valoctocogene roxaparvovec can bring to PwSHA.
Inhibition of Glycine Transporter 1 Reduces Phototoxicity in a Mouse Model of Erythropoietic Protoporphyria (EPP)
Authors: Xiang Yi , Wu Min , Chen Yue , Reisman Scott A , Venkatraman Srikanth , Yang Hua , MacDonald Brian
Published: December 2024

Erythropoietic protoporphyria (EPP) is a genetic disorder typically caused by reduced activity of ferrochelatase (FECH), the enzyme that catalyzes the final step in heme biosynthesis. EPP phototoxicity occurs when the photosensitive metal-free protoporphyrin IX (PPIX) in erythrocytes and skin is exposed to irradiation from sunlight, absorbs photons, and produces reactive oxygen species (ROS) that damage the skin and subdermal layers. Patients with EPP suffer from acute and severe phototoxicity after sun exposure, significantly impacting their quality of life.

Fech m1Pas /Fech m1Pas homozygous mice (EPP mice) retain approximately 5% residual FECH activity due to a severe homozygous loss-of-function mutation. EPP mice develop protoporphyria characterized by elevated PPIX levels in red blood cells (RBCs) and liver, which leads to liver fibrosis and cutaneous phototoxicity that manifests as skin lesions when these mice are exposed to light within the excitation wavelength of PPIX (395 to 410 nM) (Wang, 2019).

Glycine transporter 1 (GlyT1) mediates the import of glycine, a precursor for heme synthesis, to erythroid cells. The GlyT1 inhibitor bitopertin has been shown to decrease whole-blood PPIX levels in patients with EPP in Phase 2 clinical studies (Dickey, 2024; Ross, 2024) and in animal models (Wu, 2022).

This study evaluated whether GlyT1 inhibition can ameliorate phototoxicity via downregulating PPIX levels in Fechm1Pas/Fechm1Pas EPP mice. EPP mice were administered vehicle or a selective small molecule inhibitor of GlyT1, DISC-C, at 15 mg/kg by oral gavage twice daily for 18 days. GlyT1 inhibition decreased PPIX levels in RBCs by 43% and 37% on Day 14 and Day 18, respectively. On Day 14 of treatment, hair was shaved from the backs of EPP mice, and all mice were exposed to light at a wavelength of 395 nM (588±10% lumens/m2) for 30 minutes. Mice administered vehicle developed progressively worsening skin lesions with histopathological characterization of sterile abscesses, hyperkeratosis, and dermal lymphocyte infiltration. The skin lesions worsened over the observation period from Day 14 to Day 18, with 51.2% exposed skin area developing skin lesions at 4 days after light exposure (Day 18). In contrast, mice administered DISC-C developed skin lesions in 9.2% of exposed skin area, suggesting GlyT1 inhibition reduced phototoxicity in EPP mice. Additionally, a lower percentage of the area with skin lesions correlated with lower PPIX levels in RBCs.

Collectively, this study demonstrated that oral GlyT1 inhibitor administration decreased PPIX levels in RBCs, resulting in diminished phototoxicity upon light exposure in the EPP mouse model. Overall, these data support the rationale for treating patients with EPP with GlyT1 inhibitors.
Prophylactic Administration of HPA-1a-Specific Antibody RLYB212 Safely Prevents Fetal/Neonatal Alloimmune Thrombocytopenia in Pregnant Mice
Authors: Zhi Huiying , Sheridan Douglas , Newman Peter J. , Newman Debra K.
Published: December 2024

Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies targeting fetal platelet alloantigens. These alloantibodies, developed during pregnancy, lead to fetal and neonatal thrombocytopenia and, in severe cases, spontaneous or trauma-induced intracranial hemorrhage. Unlike Hemolytic Disease of the Fetus and Newborn (HDFN), which occurs in pregnancies subsequent to parturition-induced alloimmunization, an estimated 25% to 50% of FNAIT cases occur without warning during the gestation of the first pregnancy. Though long proposed, there are currently no approved therapies for the prevention of FNAIT. We have previously demonstrated that the HPA-1a-specific monoclonal antibody RLYB212 induces rapid and complete elimination of HPA-1a+ platelets from circulation and prevents alloimmunization in non-pregnant mice, making it a potential prophylactic candidate to prevent FNAIT. This study aims to evaluate the efficacy and safety of RLYB212 in preventing alloimmunization and FNAIT in pregnant mice. Wild-type (WT) female BALB/c mice were bred with HPA-1a-homozygous male C57Bl/6 mice. On days 8 and 15 after mating, pregnant females carrying HPA-1a positive fetuses were administered RLYB212 prophylactically (via IV injection) at two different doses (1.01 or 5.05 µg/kg body weight), followed by transfusion of 1.2x107 HPA-1a+ platelets (equivalent to fetal maternal hemorrhage (FMH) of ~30 ml in humans). Control mice received HPA-1a+ platelets but no RLYB212. Maternal and neonatal HPA-1a-specific alloantibody titers and neonatal platelet counts were assessed. Administration of RLYB212 at either 1.01 or 5.05 µg/kg prevented alloimmunization induced by transfusion of HPA-1a+ platelets in pregnant mice. RLYB212-treated, but not untreated, pregnant mice gave birth to pups with normal platelet counts, indicating prevention of FNAIT. In addition, the safety of administering RLYB212 during pregnancy was evaluated by monitoring pregnant mice administered RLYB212 (1.01 or 5.05 µg/kg body weight) alone without challenge with HPA-1a+ platelet transfusion. RLYB212 alone at either 1.01 or 5.05 µg/kg did not cause thrombocytopenia in HPA-1a+ pups born to treated pregnant mice. Taken together, these data establish that prophylactic administration of the HPA-1a-specific antibody RLYB212 to pregnant mice is both effective and safe in preventing maternal alloimmunization and FNAIT. These preclinical findings further support the potential of RLYB212 as a prophylactic therapy, paving the way for human studies aimed at preventing FNAIT in pregnant women.
mRNA-Laden Lipid-Nanoparticles-Enabled CD19 CAR-T Cells Engineering for the Eradication of Leukemic Cells
Authors: Chen Zhaozhao , Ren Anqi , Shu Jinhui , Li Yingying , Huang Hekuan , Hu Yu , Mei Heng
Published: December 2024

Objective: With the continuous approval and commercialization of chimeric antigen receptor T cell (CAR-T) products worldwide, CAR-T therapy has emerged as a promising approach for treating malignant tumors. However, these viral-vectors-based CAR-T cells are of close-to-prohibitive manufacturing costs, and the risks of insertional mutagenesis and secondary tumor formation. Messenger RNA (mRNA) delivery through lipid nanoparticles (LNPs) presents a novel strategy to engineer CAR-T cells, potentially reducing production costs and improving treatment-related safety, while maintaining anti-tumor activity. In this study, we developed an innovative approach for engineering CD19 CAR-T cells using mRNA-LNPs, and the anti-leukemic cells effects of CAR-T cells were validated in both in vitro and in vivo settings.

Methods: With microfluidic technology, the mRNA encoding the full humanized anti-CD19 CAR was encapsulated into mRNA-lipid nanoparticles (mRNA-LNPs) and subsequently characterized. We optimized the LNP-based transfection protocol to efficiently deliver mRNA encoding CAR constructs into T cells. The engineered CAR-T cells were then evaluated for their ability to eradicate tumor cells in vitro and in vivo. We evaluated cytokine secretion and cytotoxic activity through co-culture with target cells (Raji cells) in vitro. Furthermore, we introduced mRNA-LNP-engineered CD19 CAR-T cells into NOD-scid-IL2Rγnull (NSG) mice engrafted with Raji-luc cells, and dynamically monitored changes in tumor burden using in vivo bioluminescence imaging.

Results: Our results demonstrate that the size of the mRNA-LNPs is approximately 100 nm, and possess a negative charge, and maintain stability in PBS for 7 days. mRNA-LNPs efficiently transfect T cells, leading to high expression levels of CAR molecules (>70%), and the expression was maintained in vitro for 16 days. Moreover, CAR-T cells engineered using mRNA-LNPs exhibit potent cytotoxicity against tumor cells in vitro, as evidenced by increased tumor cell killing compared to traditional CAR-T cells. Furthermore, in a xenograft mouse model of Raji cells, administration of mRNA-LNP-enabled CAR-T cells resulted in significant tumor regression and prolonged survival period to more than 60 days of treated animals.

Conclusion: This study highlights the potential of mRNA-LNP transfection for CAR-T cell therapy in eradicating tumor cells. The innovative approach described here offers a promising strategy for improving the clinical outcomes of CAR-T cell therapy and advancing the field of cancer immunotherapy.
Outcomes of Acute Promyelocytic Leukemia (APL) during Pregnancy: A Systematic Review of Outcomes
Authors: Bahar Furkan , Ibis Betul , Bozkir Haktan Ovul , Khaddour Karam
Published: December 2024

Background: Acute promyelocytic leukemia (APL) accounts for 10-15% of all acute myeloid leukemia (AML) cases. It typically presents at a relatively early age when compared to other AML types, around the 40s.The treatment of APL) during pregnancy presents significant challenges, particularly during the first trimester due to the teratogenic effect of all-trans retinoic acid (ATRA). Standard therapy involves a combination of ATRA and arsenic trioxide (ATO), which have shown high efficacy in non-high-risk APL patients. High-risk patients typically receive induction treatment with ATRA and idarubicin (AIDA), followed by consolidation with ATRA and idarubicin/cytarabine or mitoxantrone. This systematic review aims to update the literature on the management outcomes of APL during pregnancy.

Methods: We conducted a comprehensive literature search of the PubMed database, focusing on titles and abstracts. We included case reports, case series, and retrospective cohort studies, while excluding the review articles. We identified 113 patients from 76 studies. We extracted and analyzed data on patient demographics, treatment regimens, and outcomes.

Results: The median age of the patients was 28 years (range 16-41), with a mean gestational age of 25 weeks (range 3-42). 17 patients were in the first trimester, 54 in the second trimester, and 41 in the third trimester, with one case where the trimester was not specified. Regarding induction therapy, 34 patients received ATRA only, with 27 achieving complete remission (CR) (79.41%, CI 95% : 65.83-92.99); 43 received ATRA plus chemotherapy, with 40 achieving CR (93.02%, CI 95% : 85.42-100); 20 received chemotherapy alone, with 16 achieving CR (80%, CI 95% : 62.48-97.52); and 12 received ATO with or without ATRA and/or chemotherapy, with 11 achieving CR (91.67%, CI 95% : 76.01-100). Among the 113 patients, there were 34 abortions: 15 in the first trimester, 16 in the second trimester, 2 in the third trimester, and 1 with an unspecified timing. Seventy-nine patients had deliveries, comprising 45 cesarean sections, 32 vaginal deliveries, and 2 with unspecified methods. Among patients who achieved CR, unintentional abortions occurred in 2 of 16 patients treated with chemotherapy alone, 2 of 27 treated with ATRA alone, 6 of 40 treated with ATRA plus chemotherapy, and 1 of 11 treated with ATO with or without ATRA and/or chemotherapy.

Conclusion: Managing APL during pregnancy, particularly with the advent of ATO, has shown promising outcomes, though first-trimester treatment remains complex due to teratogenic risks. Our systematic review provides updated insight into the efficacy and safety of various treatment regimens, underscoring the necessity for careful monitoring and individualized therapeutic approaches to optimize outcomes for both the mother and fetus. Further research is needed to establish standardized guidelines and improve the management of APL in pregnant patients, ensuring both maternal and fetal safety.
Temporal Single Cell Analysis of Myeloid Leukemia Microenvironment
Authors: Kaszuba Christina M , Baker Cameron D , Rodems Benjamin J , Sharma Sonali , Liesveld Jane L. , Calvi Laura M. , Becker Michael W. , Jordan Craig T , Ashton John M. , Bajaj Jeevisha
Published: December 2024

Signals from the bone marrow microenvironment are known to be critical for the support and development of adult hematopoietic stem cells (HSCs) and for leukemic initiation and progression. While niche-driven signals are known to promote cancer progression, less is known about temporal changes that occur in signal producing stromal populations during leukemia initiation and progression. To comprehensively map changes in the bone marrow microenvironmental populations, we carried out single cell RNA-sequencing in a blast crisis chronic myeloid leukemia murine model. Our temporal analysis identified 7 major stromal populations including arteriolar and sinusoidal endothelial cells, chondrocytes, fibroblasts, pericytes, mesenchymal stromal cells (MSCs), and osteo-associated cells. In particular, we note an expansion in arteriolar endothelial cells, chondrocytes and MSCs, and a loss in sinusoidal endothelial cells and osteo-associated cells. We identify changes in gene expression that may support leukemia progression, including downregulation of bone mineralization and osteoblast differentiation in MSCs, and reduced endothelial focal adhesion. This indicates that leukemic progression may be associated with an arrest in osteogenic differentiation and expansion of MSCs as well as a loss of endothelial cell integrity and function. We integrate our microenvironmental scRNA-seq data with our RNA-seq analysis of human LSCs from distinct aggressive myeloid cancer subtypes and our CRISPR based in vivo LSC dependency map to develop a temporal receptor-ligand interactome essential for disease progression. In addition to identifying key ligand-receptor interactions, our analyses identified distinct patterns of LSC-specific microenvironmental ligand expression. While the expression of some genes remained steady in the same population at all time points (e.g., Jam2 and Ihh), expression of some were lost over time (e.g. Pcdh7 and Il7), especially during disease end point. Expression of genes like Anxa1 first increased during disease progression but declined towards the end. While a fourth category of genes were expressed at all time points, the microenvironmental populations expressing them changed over time. These included Cdo1, Apoe and Agt. Importantly, we find that inhibiting expression of candidate ligands in niche cells strongly impairs the growth and survival of co-cultured leukemia cells, confirming a functional role of niche-driven ligands in disease progression. Our temporal analysis thus identifies signals that are likely necessary not only at different stages of disease progression, but also those that are critical during the entire course of the disease.
MYC Inactivation Restores Immune Surveillance in a Transgenic Mouse Model of T-Cell Acute Lymphoblastic Lymphoma
Authors: Atibalentja Danielle F , Kanakaveti Vishnupriya , Yao Lilian E , Felsher Dean W
Published: December 2024

The MYC oncogene is activated and a driving factor in the pathogenesis of many hematopoietic cancers including T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Previously, our group showed that MYC suppresses the immune system and that MYC inhibition in cancer cells can restore normal immune surveillance mechanisms through the activation of CD4+ T-cells, NK cells and innate immune responses and identified a role for Type I interferons. Now, we have performed a time-course in vivo analysis of changes in the immune system before and after experimental MYC inactivation in a transgenic mouse conditional model of MYC-driven T-ALL. Using multi-parameter flow-cytometry analysis of immune cells, we found that upon MYC activation (MYC ON) and the initiation of tumorigenesis, and upon MYC inactivation and tumor regression, there is a unique pattern of changes in CD4+ T-cells, Natural Killer cells and antigen presenting cells (APC). Specifically, we identified the expansion of immature double positive T-cells and contraction of CD4+ T-cells and NK cells in MYC ON mice with re-establishment of normal proportions of these subsets after MYC inactivation. Interestingly, in MYC ON mice, the overall frequency of MHC II positive APC was unchanged. However, there were dynamic shifts within MHC class II positive subsets associated with MYC activation including a reduction in the proportions of CD11b+Ly6C+ monocytes and F4/80+ macrophages, which were restored to normal by MYC inactivation. Finally, in MYC ON mice, we observed that splenic B-cells had increased MHC II expression that reverted to baseline following MYC inactivation. MYC ON mice additionally exhibited expansion of plasmacytoid and CD8alpha negative dendritic cells that normalized with MYC inhibition. Analysis of human T-ALL transcriptomic data further identified that MYC influences immune surveillance. Together, our results suggest that MYC may promote the development of T-ALL by altering antigen presenting cells within the tumor microenvironment possibly contributing to immune exhaustion. Inactivation of MYC thus has the potential to re-establish critical immune regulatory mechanisms.
Hidden Dangers: Pulmonary Embolism Risk in Sickle Cell Trait - Insights from the NIS Database 2020
Authors: Sanjeevi Aditya , Vijay Rao Aniket , Bhandari Samikchhya Keshary , Jose Domench Daniel Idoate , Kharel Himal
Published: December 2024

Background: Sickle cell trait is a genetic condition that occurs when an individual inherits a gene for normal hemoglobin (HbA) and a gene for sickle hemoglobin (HbS). Patients are usually asymptomatic and are diagnosed through screening tests followed by genetic analyses. In this study, we aim to compare the incidence of PE in patients with sickle trait and those without it to determine if sickle cell trait increased the risk of development of PE.

Methods: We conducted a retrospective analysis of the NIS database 2020 with an International Classification of Diseases (ICD)-10 code for sickle cell trait, PE and other comorbid conditions. STATA version SE 18.0 was used for statistical analysis. We used multivariate logistic regression models adjusting for demographic characteristics and comorbidities to determine the odds of developing PE in patients with sickle cell trait in comparison to those without it.

Results: During our study period, we noted a total number 31,766,068 hospitalizations out of which sickle cell trait hospitalizations accounted for 56,195. The median age of patients with sickle cell trait hospitalizations was 35.6 years (95% CI 35.05-36.33) and there was a female predominance. 56.39% of the patients with a sickle cell trait related hospitalization had a Charlson Comorbidity Index (CCI) of 56.39%, 17.75% had a CCI 1, 7.48% had a CCI of 2 and 18.38% had a CCI of 3. The total number of PE cases noted in the group without sickle cell trait was 181,565 while the number of PE cases in patient with sickle cell trait was 455 during the study period. We did a subgroup analysis in patients with sickle cell trait related hospitalization after adjusting for age, gender, race, CCI and the risk factors for PE such as smoking, oral contraceptive intake, obesity, history of thrombosis, thrombophilia, cancer, myeloproliferative neoplasms, fracture, COPD, and varicose veins using multivariate regression analysis. This revealed that the sickle cell trait group had higher odds of developing PE with an aOR - 1.56 (95% CI 1.26-1.94, p<0.001)

Conclusions: Our study shows that patients with sickle cell trait are at significantly increased odds of developing PE in comparison to patients without the trait. While this highlights the heightened thrombotic risk associated with sickle cell trait, we must also appreciate the fact that thus far the mechanism by which this happens is poorly understood. One proposed mechanism is tPA resistance induced by sickle cells indicating a complex interplay between various blood cell types. Further studies are needed to explore the role of sickle cell trait as a risk factor in adverse health outcomes.
The paternal influence on early childhood development in Africa: implications for child and adolescent mental health
Authors: Osborne Augustus , Ahinkorah Bright Opoku
Published: December 2024

This commentary examines the influence of fathers in early childhood development in Africa and its implications for child and adolescent mental health. Historically overshadowed by maternal influence, research increasingly highlights the multifaceted impact of paternal involvement on children’s cognitive, emotional, social, and behavioural development. Fathers contribute uniquely to children’s mental growth through stimulating play and rich language interaction. Their emotional engagement fosters children’s self-esteem and resilience. Moreover, fathers influence social skills by modelling interactions and encouraging exploration. Paternal involvement is linked to improved behaviour regulation. Beyond direct interaction, factors such as paternal mental health, economic stability, and co-parenting dynamics also shape child outcomes. Despite the impact of engaged fatherhood on children’s cognitive, emotional, and social development, many fathers encounter barriers such as economic pressures, cultural norms, and migration. These challenges often hinder their ability to participate actively in their children’s lives, resulting in a disconnect that can affect family dynamics and child well-being. Addressing cultural and societal barriers to father involvement is crucial to optimise child development. To address these issues, the paper outlines several key policy implications aimed at promoting paternal involvement. This commentary serves as a foundation for further exploration of fathers’ complex and vital role in shaping children's lives.
Multimodal genome-wide survey of progressing and non-progressing breast ductal carcinoma in-situ
Authors: Debeljak Marija , Cho Soonweng , Downs Bradley M. , Considine Michael , Avin-McKelvey Brittany , Wang Yongchun , Perez Phillip N. , Grizzle William E. , Hoadley Katherine A. , Lynch Charles F. , Hernandez Brenda Y. , van Diest Paul J. , Cozen Wendy , Hamilton Ann S. , Hawes Debra , Gabrielson Edward , Cimino-Mathews Ashley , Florea Liliana D. , Cope Leslie , Umbricht Christopher B.
Published: December 2024

Background

Ductal carcinoma in-situ (DCIS) is a pre-invasive form of invasive breast cancer (IBC). Due to improved breast cancer screening, it now accounts for ~ 25% of all breast cancers. While the treatment success rates are over 90%, this comes at the cost of considerable morbidity, considering that the majority of DCIS never become invasive and our understanding of the molecular changes occurring in DCIS that predispose to invasive disease is limited. The aim of this study is to characterize molecular changes that occur in DCIS, with the goal of improving DCIS risk stratification.

Methods

We identified and obtained a total of 197 breast tissue samples from 5 institutions (93 DCIS progressors, 93 DCIS non-progressors, and 11 adjacent normal breast tissues) that had at least 10-year follow-up. We isolated DNA and RNA from archival tissue blocks and characterized genome-wide mRNA expression, DNA methylation, DNA copy number variation, and RNA splicing variation.

Results

We obtained all four genomic data sets in 122 of the 197 samples. Our intrinsic expression subtype-stratified analyses identified multiple molecular differences both between DCIS subtypes and between DCIS and IBC. While there was heterogeneity in molecular signatures and outcomes within intrinsic subtypes, several gene sets that differed significantly between progressing and non-progressing DCIS were identified by Gene Set Enrichment Analysis.

Conclusion

DCIS is a molecularly highly heterogenous disease with variable outcomes, and the molecular events determining DCIS disease progression remain poorly defined. Our genome-wide multi-omic survey documents DCIS-associated alterations and reveals molecular heterogeneity within the intrinsic DCIS subtypes. Further studies investigating intrinsic subtype-stratified characteristics and molecular signatures are needed to determine if these may be exploitable for risk assessment and mitigation of DCIS progression. The highly significant associations of specific gene sets with IBC progression revealed by our Gene Set Enrichment Analysis may lend themselves to the development of a prognostic molecular score, to be validated on independent DCIS cohorts.
Rore: robust and efficient antioxidant protein classification via a novel dimensionality reduction strategy based on learning of fewer features
Authors: Meng Chaolu , Hou Yongqi , Zou Quan , Shi Lei , Su Xi , Ju Ying
Published: December 2024

In protein identification, researchers increasingly aim to achieve efficient classification using fewer features. While many feature selection methods effectively reduce the number of model features, they often cause information loss caused by merely selecting or discarding features, which limits classifier performance. To address this issue, we present Rore, an algorithm based on a feature-dimensionality reduction strategy. By mapping the original features to a latent space, Rore retains all relevant feature information while using fewer representations of the latent features. This approach significantly preserves the original information and overcomes the information loss problem associated with previous feature selection. Through extensive experimental validation and analysis, Rore demonstrated excellent performance on an antioxidant protein dataset, achieving an accuracy of 95.88% and MCC of 91.78%, using vectors including only 15 features. The Rore algorithm is available online at http://112.124.26.17:8021/Rore.
Remission of Insulin-Dependent Diabetes Mellitus in Multiple Endocrine Neoplasia Type 2A After Adrenalectomy
Authors: Sato Megumi , Otsuki Michio , Mori Tomomi , Yanagida Juro , Yamamoto Toshiyuki , Nakagami Tomoko
Published: December 2024

A 37-year-old man presented with symptoms of polyuria and weight loss over the past year. Initial laboratory examination showed elevated blood glucose level (468 mg/dL [25.9 mmol/L]; normal reference range [RR], 75-109 mg/dL [4.1-6.0 mmol/L]), high glycated hemoglobin A1c (13.2% [120 mmol/mol]; RR, 4.6-6.2% [26-44 mmol/mol]), low urinary C-peptide excretion (17.4 μg/day [5.76 nmol/day]; RR, 18.3-124.4 μg/day [6.0-41.1 nmol/day]), and ketosis, leading to a diagnosis of insulin-dependent diabetes mellitus. Subsequent investigations identified medullary thyroid carcinoma and bilateral pheochromocytomas. Given the detected RET gene variant and the patient's family history of multiple endocrine neoplasia type 2A (MEN2A), the diagnosis of MEN2A was confirmed. Upon hospital admission, intensive insulin therapy was commenced, which resolved the symptoms and normalized blood glucose levels. Subsequently, laparoscopic bilateral adrenalectomy was performed, after which the patient's glucose tolerance normalized, eliminating the need for diabetes treatment and avoiding hypoglycemia. This case highlights the potential for catecholamine-induced suppression of insulin secretion via α2 action on pancreatic β-cells to be remission and rapidly improved by adrenalectomy in individuals with MEN2A experiencing insulin-dependent diabetes mellitus.
Safety Net Spending on Children and the Sources of Household Income Across U.S. States, 1997–2016
Authors: Jackson Margot I. , Wimer Christopher , Zilkha Chloe
Published: December 2024

High levels of poverty and economic precarity in the United States relative to other countries have led to academic and policy debates about whether welfare state investments accomplish what they are intended to. Although social safety net spending clearly has antipoverty effects at the national level, there is scant evidence on the “resource pathway” presumed to underlie the effects of the local welfare state on families with children. Which types of public investments have especially contributed to the total resources of households with children? Understanding this question at the state level is important, given dramatic variation in states’ safety net spending on children and the rise of federalism, which increases state autonomy in designing and administering social programs. Using annual data from the 1997–2016 State-by-State Spending on Kids Dataset linked to data from the Census Bureau's Annual Social and Economic Supplement to the Current Population Survey, we examine the relationship between transfer spending in states and household income sources. Findings suggest that government transfers raise the total income of households with the lowest income and educational levels and that transfer income among these households is more multidimensional than among higher resource households. Further, analyses using variation within and across states demonstrate that state-level spending in each area is associated with an increase in corresponding transfer income among non-college-educated households and those in the bottom half of the income distribution; such spending is associated with no increase (or a decrease) in transfer income among college-educated households and those in the top quarter of the income distribution. These results suggest that increases in state-level spending disproportionately benefit the budgets of households with the lowest resources and might be a promising means to reduce resource gaps between households.
Το νέο πρόγραμμα σπουδών Φυσικών Δημοτικού
Authors: Κώτσης Κωνσταντίνος Θ. , Γκικοπούλου Ουρανία , Πατρινόπουλος Ματθαίος , Μιτζήθρας Κωνσταντίνος , Αποστολάκης Εμμανουήλ , Καλκάνης Γεώργιος Θ.
Published: December 2024

Το 2021 ολοκληρώθηκε η σύνταξη του νέου Προγράμματος Σπουδών για τα Φυσικά Δημοτικού (Ε’ και Στ’ τάξη), σε συνεργασία με τους επόπτες/εκπονητές των Π.Σ. Φυσικής Γυμνασίου και Λυκείου, ώστε να περιλαμβάνουν μερικές «βασικές» θεματικές ενότητες, που διατρέχουν όλες τις βαθμίδες, σταδιακά εμπλουτιζόμενες και λαμβάνοντας υπόψη τα νεότερα πορίσματα της επιστήμης. Βασικό ρόλο στην εκπαιδευτική διαδικασία, σύμφωνα με τη διερευνητική επιστημονική-εκπαιδευτική μεθοδολογία, έχει ο αποδεικτικός πειραματισμός και η μάθηση αντιμετωπίζεται ολιστικά και όχι αποσπασματικά με την αξιοποίηση διαθεματικών / διεπιστημονικών πληροφοριών και τη χρήση ένθετων κειμένων και πρόσθετου ψηφιακού υλικού που ενημερώνουν τους μαθητές για τεχνολογικά επιτεύγματα και εξασκούν την κριτική τους ικανότητα και τον ορθολογικό τρόπο σκέψης. Το Νέο Π.Σ. Φυσικών παρέχει στους μαθητές κίνητρα αλλά και τη δυνατότητα να αποκτούν, εκτός από γνώσεις, δεξιότητες και να διαμορφώνουν στάσεις απαραίτητες για τους πολίτες του 21ου αιώνα. Στην εργασία παρουσιάζεται η στοχοθεσία του νέου Π.Σ., η φιλοσοφία εκπόνησής του, τα βασικά καινοτομικά στοιχεία του, η προτεινόμενη μεθοδολογία και καλές πρακτικές καθώς και τα βασικά αποτελέσματα από την πιλοτική εφαρμογή του στα Πειραματικά Σχολεία.
Εισάγοντας την έννοια της βαρύτητας κατά τον Einstein στην πρωτοβάθμια εκπαίδευση: Σύγκριση επιδόσεων ανάλογα με το φύλο των μαθητών
Authors: Βακάρου Γεωργία , Κώτσης Κωνσταντίνος Θ.
Published: December 2024

Η πιο πρόσφατη θεωρία που περιγράφει την έννοια της βαρύτητας είναι η Γενική Θεωρία της Σχετικότητας που διατυπώθηκε από τον Albert Einstein. Η διδασκαλία αυτής της θεωρίας αγνοείται από τη σχολική πραγματικότητα. Η παρούσα έρευνα εξετάζει, μέσω ενός γραπτού ερωτηματολογίου, τις επιδόσεις 83 μαθητών/τριων της ΣΤ τάξης του Δημοτικού, πριν και μετά από μία διδακτική παρέμβαση που αφορά στην έννοια της βαρύτητας όπως αυτή διατυπώνεται στη Σύγχρονη Φυσική. Επιπλέον, γίνεται ανάλυση των αποτελεσμάτων ανάλογα με το φύλο των μαθητών. Τα αποτελέσματα υποδεικνύουν εννοιολογική κατανόηση και μη στατιστικά σημαντική διαφορά ανάλογα με το φύλο των μαθητών.
Ετοιμότητα και στάσεις εκπαιδευτικών Φυσικών Επιστημών ως προς τη διδασκαλία της Κβαντικής Φυσικής
Authors: Χούσου Πηνελόπη , Σίμος Θωμάς
Published: December 2024

Το 2023 οι μαθητές της Γ΄Λυκείου της ομάδας προσανατολισμού θετικών σπουδών και σπουδών υγείας εξετάζονται για πρώτη φορά πανελλαδικά σε στοιχεία κβαντικής φυσικής (ΚΦ). Η διδασκαλία της ΚΦ μπορεί ωστόσο να χαρακτηριστεί ως μια πρόκληση για τους εκπαιδευτικούς, γιατί η παραδοσιακή αφηγηματική προσέγγιση στο συγκεκριμένο θέμα ίσως δεν επαρκεί, ώστε οι μαθητές να αποκτήσουν μια εννοιολογική κατανόηση των θεμελιωδών αρχών αλλά και γιατί οι ίδιοι οι εκπαιδευτικοί βρίσκονται αντιμέτωποι με την διδασκαλία της για πρώτη φορά.
Στην παρούσα μελέτη γίνεται προσπάθεια να εξακριβωθεί το επίπεδο ετοιμότητας και να καταγράφουν οι στάσεις των εκπαιδευτικών φυσικών επιστήμων στην διδασκαλία της ΚΦ. Πραγματοποιήθηκε ποσοτική μελέτη με δείγμα 84 καθηγητών Φυσικής και Χημείας. Ως ερευνητικό εργαλείο χρησιμοποιήθηκε το Teacher Readiness to teach Quantum Physics (TRQP) με αξιοπιστία 0,81. Τα ευρήματα της μελέτης δείχνουν ότι η ετοιμότητα των φυσικών είναι υψηλή, ενώ των χημικών μέτρια και ότι και οι δυο ειδικότητες διαθέτουν θετικές στάσεις όσο αφορά την διδασκαλία της ΚΦ. Τα αποτελέσματα αυτής της μελέτης μπορούν να βοηθήσουν τους υπεύθυνους χάραξης πολιτικής και το Υπουργείο Παιδείας να κατανοήσουν καλύτερα την τρέχουσα κατάσταση σχετικά με την διδασκαλία της ΚΦ.
Εναλλακτικές ιδέες προπτυχιακών φοιτητών/τριων Δημοτικής Εκπαίδευσης για το υδατικό αποτύπωμα
Authors: Γκίτσας Στέργιος , Μαλανδράκης Γεώργιος , Θεοδοσίου Νικόλαος , Λαμπρινός Νικόλαος
Published: December 2024

Οι ανθρώπινες δραστηριότητες χρησιμοποιούν και ρυπαίνουν μεγάλες ποσότητες νερού. H χρήση της μεθοδολογίας του Υδατικού Αποτυπώματος (ΥΑ) μπορεί να βοηθήσει στην καλύτερη διαχείριση του νερού από τα άτομα και τις κυβερνήσεις. Η παρούσα έρευνα είχε ως σκοπό τη συλλογή πληροφοριών σχετικά με τις εναλλακτικές αντιλήψεις προπτυχιακών εκπαιδευτικών από Παιδαγωγικά Τμήματα Δημοτικής Εκπαίδευσης για το ΥΑ.  Τα δεδομένα της έρευνας συλλέχθηκαν μέσω ηλεκτρονικού ερωτηματολογίου 9 Ερωτήσεων, το οποίο συμπληρώθηκε από 64 φοιτητές/τριες. Πραγματοποιήθηκε ανάλυση περιεχομένου στις απαντήσεις των φοιτητών/τριών με μονάδα ανάλυσης τη μονάδα νοήματος. Η ανάλυση περιεχομένου φανέρωσε πολλές εναλλακτικές αντιλήψεις και παρανοήσεις των συμμετεχόντων σχετικά με τον εννοιολογικό προσδιορισμό του ΥΑ.
Καλλιέργεια των κοινωνικών-αειφορικών αξιών στην περιβαλλοντική εκπαίδευση/ εκπαίδευση για την αειφόρο ανάπτυξη μέσα από επίμαχα τοπικά ζητήματα. Η περίπτωση της απολιγνιτοποίησης στη Δυτική Μακεδονία
Authors: Θεοφανίδου Ελένη , Παπαδοπούλου Πηνελόπη
Published: December 2024

Στην παρούσα εργασία διερευνώνται οι αντιλήψεις των εκπαιδευτικών για το αξιακό πλαίσιο της αειφορίας καθώς και το εάν τα προγράμματα Περιβαλλοντικής Εκπαίδευσης/Εκπαίδευσης για την Αειφόρο Ανάπτυξη (ΠΕ/ΕΑΑ) που σχετίζονται με επίμαχα τοπικά ζητήματα, όπως η απολιγνιτοποίηση στη Δυτική Μακεδονία, μπορούν να προωθήσουν τις αξίες αυτές συμβάλλοντας στην ενεργό πολιτειότητα και στη συμμετοχή των μαθητών σε διαδικασίες λήψης αποφάσεων στο μέλλον. Η έρευνα διενεργήθηκε μέσω ημιδομημένων συνεντεύξεων με 18 εκπαιδευτικούς σύμφωνα με την προσέγγιση της Θεμελιωμένης Θεωρίας (ΘΘ). Τα ευρήματα έδειξαν ότι η ΠΕ/ΕΑΑ και οι εκπαιδευτικοί συμβάλλουν θετικά προς αυτήν την κατεύθυνση παρόλο που η εκπόνηση προγραμμάτων σχετιζόμενα με ακανθώδη ζητήματα της τοπικής κοινωνίας αποτελεί δύσκολο εγχείρημα.
Κριτική αποτίμηση του επιστημονικού πεδίου της Φύσης της Επιστήμης (ΦτΕ) και αναζήτηση συνεργειών με μία εναλλακτική ατζέντα για τη φύση των επιστημών (ΦτΕν)
Authors: Σχίζας Δημήτριος
Published: December 2024

Η παρούσα εργασία εξετάζει την βιβλιογραφία γύρω από την τρέχουσα συναινετική ατζέντα της Φύσης της Επιστήμης μέσα από μια επιστημολογική οπτική και συμπεραίνει ότι το εν λόγω επιστημονικό πεδίο στο χώρο της Διδακτικής των Φυσικών Επιστημών δεν έχει αρκετά ισχυρή εξηγητική δύναμη λόγω του τρόπου με τον οποίο είναι δομημένο. Στη συνέχεια, προσπαθεί να δείξει το πώς μια εναλλακτική ατζέντα της Φύσης των Επιστημών που θα επικεντρώνεται στα μοναδικά επιστημολογικά χαρακτηριστικά της κάθε επιστήμης μπορεί να βοηθήσει το πεδίο να ξεπεράσει το επιστημολογικό του αυτό πρόβλημα.
Διδακτικός σχεδιασμός για το Φως & πιλοτική εφαρμογή σύμφωνα με τα νέα αναλυτικά προγράμματα σπουδών στη Γ' τάξη του Δημοτικού
Authors: Τσιούρη Ελευθερία , Γκουλγκούτη Αναστασία , Τσιχουρίδης Χαρίλαος
Published: December 2024

Στην εργασία παρουσιάζεται μια διδακτική πρακτική για τη διδασκαλία του φωτός στη Γ΄ τάξη του Δημοτικού σχολείου, η οποία βασίζεται στις αρχές και στους στόχους των Νέων Προγραμμάτων Σπουδών της Μελέτης Περιβάλλοντος. Από την πιλοτική εφαρμογή που πραγματοποιήθηκε σε 24 μαθητές/τριες της Γ΄ τάξης του 1ου Πειραματικού Δημοτικού Σχολείου Ιωαννίνων φαίνεται η ανάγκη για την αναθεώρηση των έως σήμερα μεθόδων διδασκαλίας και την εισαγωγή των ΝΠΣ της Μελέτης Περιβάλλοντος σε όλες τις σχολικές μονάδες.
Διδασκαλία εννοιών Φυσικών Επιστημών και καλλιέργεια ήπιων δεξιοτήτων κατά την προετοιμασία μαθητών Δευτεροβάθμιας σε διαγωνισμό STEM
Authors: Κουμαρά Άννα , Πολάτογλου Χαρίτων
Published: December 2024

Στην παρούσα εργασία παρουσιάζεται η διδασκαλία εννοιών των Φυσικών Επιστημών και καλλιέργειας ήπιων δεξιοτήτων κατά την προετοιμασία 14 μαθητών Δευτεροβάθμιας Εκπαίδευσης σε διαγωνισμό Εκπαιδευτικής Ρομποτικής, όπου έπρεπε να κατασκευάσουν το δικό τους ρομπότ. Οι μαθητές χωρίστηκαν σε πέντε ομάδες, και δούλεψαν για έξι μήνες. Από τις έννοιες των Φυσικών Επιστημών κατανόησαν την έννοια της αδράνειας και της ταχύτητας. Ταυτόχρονα ανέπτυξαν τις δεξιότητες της δημιουργικότητας, της επικοινωνίας, της συνεργασίας και της κριτικής σκέψης. Η μέτρηση της εξέλιξης των δεξιοτήτων έγινε με δημιουργία κατάλληλης ρουμπρίκας, όπου φάνηκε ότι όλες οι ομάδες εξελίχθηκαν, σε διαφορετικό βαθμό η καθεμία. Οι έννοιες των Φ.Ε. εξετάστηκαν με ανάλυση συνεντεύξεων των μαθητών για σωστή χρήση στο λόγο τους.
Αξιολογώντας τις δεξιότητες διερεύνησης μαθητών Γυμνασίου με την εμπλοκή τους σε διερευνητικά φύλλα εργασίας
Authors: Πετρίδου Ελένη , Μολοχίδης Αναστάσιος , Χατζηκρανιώτης Ευριπίδης
Published: December 2024

Στην εργασία παρουσιάζεται η ανάπτυξη μιας διερευνητικής διδακτικής μαθησιακής ακολουθίας βασισμένης στο συνεχές της διερεύνησης. Οι μαθητές εμπλέκονται σε πειραματικές δραστηριότητες με διαδικτυακές προσομοιώσεις ολοένα μικρότερης καθοδήγησης. Στόχος της εργασίας είναι η αξιολόγηση της ικανότητας των μαθητών να εφαρμόζουν τις φάσεις της διερεύνησης σε γνωστικό αντικείμενο διαφορετικό από αυτό στο οποίο τις έχουν διδαχθεί. Τα αποτελέσματα δείχνουν ότι οι δεξιότητες διερεύνησης μπορούν να διδαχθούν, αν και κάποιοι μαθητές δυσκολεύονται να εφαρμόσουν όλες τις φάσεις της διερεύνησης δίχως καθοδήγηση.
Διδακτικός σχεδιασμός για τη χώρα μου & πιλοτική εφαρμογή σύμφωνα με τα νέα αναλυτικά προγράμματα σπουδών στη Γ’ τάξη του Δημοτικού
Authors: Τσιούρη Ελευθερία , Γκουλγκούτη Αναστασία , Πανταζής Σπυρίδων
Published: December 2024

Τα Προγράμματα Σπουδών αποτελούν ένα αναπόσπαστο κομμάτι της εκπαιδευτικής διαδικασίας. Γίνεται μεγάλη συζήτηση για τα Προγράμματα Σπουδών που θα εκπαιδεύουν τους αυριανούς μαθητές, προετοιμάζοντάς τους με γνώσεις και δεξιότητες για να γίνουν οι αυριανοί ενεργοί πολίτες. Στην παρούσα εργασία παρουσιάζεται ο διδακτικός σχεδιασμός για τη θεματική ενότητα «Η χώρα που ζω», έτσι όπως αυτός σχεδιάστηκε και υλοποιήθηκε πιλοτικά, σύμφωνα με τα Νέα Αναλυτικά Προγράμματα Σπουδών της Μελέτης Περιβάλλοντος στην Γ΄ Τάξη του 1ου Πειραματικού Δημοτικού Σχολείου Ιωαννίνων για το σχολικό έτος 2022-2023. Η συγκεκριμένη ενότητα αντλεί θέματα και έννοιες από τη Γεωγραφία.
Aethonas Adventure: Ψηφιακό παιχνίδι επαυξημένης πραγματικότητας (AR) για τον αειφορικό μεσογειακό τρόπο ζωής
Authors: Χατζηνικόλα Χαριστούλα , Μαρκουζής Δημήτριος , Παπαβασιλείου Βασίλειος
Published: December 2024

Οι παραδοσιακές διατροφικές συνήθειες των λαών της Μεσογείου συνδέονται με έναν τρόπο ζωής που χαρακτηρίζεται από μακροζωία, απουσία άγχους, ευθυμία, αυξημένη φυσική δραστηριότητα, στενή επαφή και σύνδεση με τον πολιτισμό και τη φύση. Στην παρούσα έρευνα δημιουργήθηκε ένα παιχνίδι επαυξημένης πραγματικότητας για φορητές συσκευές με σκοπό τη βελτίωση των γνώσεων των μαθητών/τριών για τον αειφορικό Μεσογειακό τρόπο ζωής στην κοιλάδα του Αίθωνα στη Ρόδο. Για τη δημιουργία του παιχνιδιού εφαρμόστηκε η συμμετοχική μέθοδος με δέκα μαθητές/τριες γυμνασίου και δύο εκπαιδευτικούς. Τα αποτελέσματα ήταν ενθαρρυντικά, καθώς οι μαθητές/τριες βελτίωσαν τις γνώσεις τους και διατήρησαν σε υψηλό επίπεδο τη συγκέντρωση και τη συμμετοχή τους κατά την εκπαιδευτική διαδικασία.