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Abstract The search for understanding immunotherapy response has sparked interest in diverse areas of oncology, with artificial intelligence (AI) and radiomics emerging as promising tools, capable of gathering large amounts of information to identify suitable patients for treatment. The application of AI in radiology has grown, driven by the hypothesis that radiology images capture tumor phenotypes and thus could provide valuable insights into immunotherapy response likelihood. However, despite the rapid growth of studies, no algorithms in the field have reached clinical implementation, mainly due to the lack of standardized methods, hampering study comparisons and reproducibility across different datasets. In this review, we performed a comprehensive assessment of published data to identify sources of variability in radiomics study design that hinder the comparison of the different model performance and, therefore, clinical implementation. Subsequently, we conducted a use-case meta-analysis using homogenous studies to assess the overall performance of radiomics in estimating programmed death-ligand 1 (PD-L1) expression. Our findings indicate that, despite numerous attempts to predict immunotherapy response, only a limited number of studies share comparable methodologies and report sufficient data about cohorts and methods to be suitable for meta-analysis. Nevertheless, although only a few studies meet these criteria, their promising results underscore the importance of ongoing standardization and benchmarking efforts. This review highlights the importance of uniformity in study design and reporting. Such standardization is crucial to enable meaningful comparisons and demonstrate the validity of biomarkers across diverse populations, facilitating their implementation into the immunotherapy patient selection process.

Abstract Chimeric antigen receptor (CAR) T‐cell therapy is a promising treatment option for relapsed or refractory (R/R) large B‐cell lymphoma (LBCL). However, only a subset of patients will present long‐term benefit. In this study, we explored the potential of PET‐based radiomics to predict treatment outcomes with the aim of improving patient selection for CAR T‐cell therapy. We conducted a single‐center study including 93 consecutive R/R LBCL patients who received a CAR T‐cell infusion from 2018 to 2021, split in training set (73 patients) and test set (20 patients). Radiomics features were extracted from baseline PET scans and clinical benefit was defined based on median progression‐free survival (PFS). Cox regression models including the radiomics signature, conventional PET biomarkers and clinical variables were performed for most relevant outcomes. A radiomics signature including 4 PET‐based parameters achieved an AUC = 0.73 for predicting clinical benefit in the test set, outperforming the predictive value of conventional PET biomarkers (total metabolic tumor volume [TMTV]: AUC = 0.66 and maximum standardized uptake value [SUVmax]: AUC = 0.59). A high radiomics score was also associated with longer PFS and OS in the multivariable analysis. In conclusion, the PET‐based radiomics signature predicted efficacy of CAR T‐cell therapy and outperformed conventional PET biomarkers in our cohort of LBCL patients.

Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease. However, patients’ outcomes are heterogenous, and there is lack of validated predictive biomarkers of response, while biomarkers for early identification of patients who benefit from treatment are limited. This case report describes a remarkable and durable response to Ra-223 in a CRPC patient with bone metastases who had rapidly progressed to many previous therapies; this response is now lasting for 5 years even after having stopped backbone androgen deprivation therapy (ADT). Here, we present the clinical course of this exceptional response, as well as comprehensive genomic and histopathology analyses on sequential biopsies acquired before and after therapy. Additionally, we review current knowledge on predictive and response biomarkers to Ra-223 in metastatic prostate cancer.

Abstract Tumor heterogeneity has been postulated as a hallmark of treatment resistance and a cure constraint in cancer patients. Conventional quantitative medical imaging (radiomics) can be extended to computing voxel-wise features and aggregating tumor subregions with similar radiological phenotypes (imaging habitats) to elucidate the distribution of tumor heterogeneity within and among tumors. Despite the promising applications of imaging habitats, they may be affected by variability of radiomics features, preventing comparison and generalization of imaging habitats techniques. We performed a comprehensive repeatability and reproducibility analysis of voxel-wise radiomics features in more than 500 lung cancer patients with computed tomography (CT) images and demonstrated the effect of voxel-wise radiomics variability on imaging habitats computation in 30 lung cancer patients with test–retest images. Repeatable voxel-wise features characterized texture heterogeneity and were reproducible regardless of the applied feature extraction parameters. Imaging habitats computed using robust radiomics features were more stable than those computed using all features in test–retest CTs from the same patient. Nine voxel-wise radiomics features (joint energy, joint entropy, sum entropy, maximum probability, difference entropy, Imc1, Imc2, Idn and Idmn) were repeatable and reproducible. This supports their application for computing imaging habitats in lung tumors towards the discovery of previously unseen tumor heterogeneity and the development of novel non-invasive imaging biomarkers for precision medicine.

Abstract Glioblastoma is the most common primary brain tumor. Standard therapy consists of maximum safe resection combined with adjuvant radiochemotherapy followed by chemotherapy with temozolomide, however prognosis is extremely poor. Assessment of the residual tumor after surgery and patient stratification into prognostic groups (i.e., by tumor volume) is currently hindered by the subjective evaluation of residual enhancement in medical images (magnetic resonance imaging [MRI]). Furthermore, objective evidence defining the optimal time to acquire the images is lacking. We analyzed 144 patients with glioblastoma, objectively quantified the enhancing residual tumor through computational image analysis and assessed the correlation with survival. Pathological enhancement thickness on post-surgical MRI correlated with survival (hazard ratio: 1.98, p

Handwriting is a complex activity that involves continuous interaction between lower-level handwriting and motor skills and higher-order cognitive processes. It is important to allocate mental resources to these high-order processes since these processes place a great demand on cognitive capacity. This is possible when lower-level skills such as transcription are effortlessness and fluent. Given that fluency is a value in virtually all areas of academic learning, schools should provide instructional activities to promote writing fluency from the first stages of learning to write. In an effort to determine if teaching handwriting enhances writing fluency, we conducted a systematic and meta-analytic review of the writing fluency intervention literature. We selected 31 studies: 21 true and quasi-experimental studies, 4 single-group design, 3 single-subject design, and 3 non-experimental studies, conducted with K-6 students in a regular school setting. A total of 2,030 students participated in these studies. When compared to no instruction or non-handwriting instructional conditions, teaching different handwriting intervention programs resulted in statistically significant greater writing fluency (ES = 0.64). Moreover, three specific handwriting interventions yielded statistically significant results in improving writing fluency, when compared to other handwriting interventions or to typical handwriting instruction conditions: handwriting focused on training timed transcription skills (ES = 0.49), multicomponent handwriting treatments (ES = 0.40), and performance feedback (ES = 0.36). There were not enough data to calculate the impact of sensory-motor and self-regulated strategy handwriting interventions on writing fluency. The significance of these findings for implementing and differentiating handwriting fluency instruction and guiding future research will be discussed.

Climate change requires the designing of strategies that mitigate the damage to people’s daily life. One of the most notable consequences of climate change in the Iberian Peninsula is flooding, the frequency and social and economic impact of which have increased in recent decades. As a result, a change of paradigm in flood risk management has been identified, with the social dimension of the disasters acquiring more importance. This paper presents a review of the theoretical and empirical approaches in relation to flood risk, emphasizing the contributions made in the field of environmental psychology. Two main objectives are pursued: to build an appropriate conceptual framework for the analysis of flood risk and to provide professionals in this field with the necessary practical resources to deal with problems that require psycho-socioenvironmental intervention.

The tumour immune microenvironment influences the efficacy of immune checkpoint inhibitors. Within this microenvironment are CD8-expressing tumour-infiltrating lymphocytes (CD8+ TILs), which are an important mediator and marker of anti-tumour response. In practice, the assessment of CD8+ TILs via tissue sampling involves logistical challenges. Radiomics, the high-throughput extraction of features from medical images, may offer a novel and non-invasive alternative. We performed a systematic review of the available literature reporting radiomic signatures associated with CD8+ TILs. We also aimed to evaluate the methodological quality of the identified studies using the Radiomics Quality Score (RQS) tool, and the risk of bias and applicability with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Articles were searched from inception until 31 December 2021, in three electronic databases, and screened against eligibility criteria. Twenty-seven articles were included. A wide variety of cancers have been studied. The reported radiomic signatures were heterogeneous, with very limited reproducibility between studies of the same cancer group. The overall quality of studies was found to be less than desirable (mean RQS = 33.3%), indicating a need for technical maturation. Some potential avenues for further investigation are also discussed.

Studies have shed light on the idea that people who have experiences in natural settings might be more aware of the environment. Learning gardens, as outdoor contexts, might contribute to the development of students’ affective relations toward nature, pro-environmental attitudes, and protective actions; neverthless, these aspects begging to be explored. This preliminary research investigates the impact that the use of organic gardens to teach natural sciences at university has on kindergarten pre-service teachers’ (KPST) connectedness to and conceptions of nature. The research follows a pre-/post-design and it uses a mixed methods approach. A total of 74 students completed four quantitative scales (INS, CCC, LCN, and NR-6), and 66 of them an open question about the concept of nature. After the garden experience, students scored higher in all the scales, nevertheless the change was significant only for INS and CCC. The phenomenographic analysis evidenced an initial predominant static and non-social concept of nature, biased toward the most obvious biological elements. After the garden-based learning experience, more informed conceptions of nature – including notions of complexity and systemic character – increased from 7 to 19%; however, statistical comparison was not significant. In spite of the absence of concluding results, further research is required to assess the role that learning gardens may play regarding connectedness to nature and pro-environmental behaviors.