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Purpose: To evaluate the ability of preoperative MRI-based measurements to predict the pathological T (pT) stage and cervical lymph node metastasis (CLNM) via machine learning (ML)-driven models trained in oral tongue squamous cell carcinoma (OTSCC). Materials and methods: 108 patients with a new diagnosis of OTSCC were enrolled. The preoperative MRI study included post-contrast high-resolution T1-weighted images acquired in all patients. MRI-based depth of invasion (DOI) and tumor dimension—together with shape-based and intensity-based features—were extracted from the lesion volume segmentation. The entire dataset was randomly divided into a training set and a validation set, and the performances of different types of ML algorithms were evaluated and compared. Results: MRI-based DOI and tumor dimension together with several shape-based and intensity-based signatures significantly discriminated the pT stage and LN status. The overall accuracy of the model for predicting the pT stage was 0.86 (95%CI, 0.78–0.92) and 0.81 (0.64–0.91) in the training and validation sets, respectively. There was no improvement in the model performance upon including shape-based and intensity-based features. The model for predicting CLNM based on DOI and tumor dimensions had a fair accuracy of 0.68 (0.57–0.78) and 0.69 (0.51–0.84) in the training and validation sets, respectively. The shape-based and intensity-based signatures have shown potential for improving the model sensitivity, with a comparable accuracy. Conclusion: MRI-based models driven by ML algorithms could stratify patients with OTSCC according to the pT stages. They had a moderate ability to predict cervical lymph node metastasis.

Abstract NAVIGATOR is an Italian regional project boosting precision medicine in oncology with the aim of making it more predictive, preventive, and personalised by advancing translational research based on quantitative imaging and integrative omics analyses. The project’s goal is to develop an open imaging biobank for the collection and preservation of a large amount of standardised imaging multimodal datasets, including computed tomography, magnetic resonance imaging, and positron emission tomography data, together with the corresponding patient-related and omics-related relevant information extracted from regional healthcare services using an adapted privacy-preserving model. The project is based on an open-source imaging biobank and an open-science oriented virtual research environment (VRE). Available integrative omics and multi-imaging data of three use cases (prostate cancer, rectal cancer, and gastric cancer) will be collected. All data confined in NAVIGATOR (i.e., standard and novel imaging biomarkers, non-imaging data, health agency data) will be used to create a digital patient model, to support the reliable prediction of the disease phenotype and risk stratification. The VRE that relies on a well-established infrastructure, called D4Science.org, will further provide a multiset infrastructure for processing the integrative omics data, extracting specific radiomic signatures, and for identification and testing of novel imaging biomarkers through big data analytics and artificial intelligence.

Variations of environmental parameters, like thermo-hygrometric, acoustic, visual and indoor air quality can influence the sensitivities of individuals on the spectrum. This paper presents research on this issue, studied by means of questionnaires administered to parents and professional caregivers taking care of people with Autism Spectrum Disorder (ASD).The study highlights that there are clear differences if the indirect evaluations are performed by parents or professional caregivers, in relation to the specific identification of stress sources. Additionally, acoustic domain is identified as the one causing the major stress, especially caused by strong noises and particular sounds such as voices, animal sounds and impacts, and its dependence on the severity of autism is evidenced. Furthermore, a lower impact of thermal, visual and IAQ factors is determined, with the exception of some specific stimuli like light contrast (glare), high illumination, particular light sources or stale air. Finally, this paper provides evidence of the influence of age, severity of autism and co-morbidities on perceived stress.

The present study applies an approach to analyze the stress induced on people on the autism condition. Dedicated questionnaires were prepared, in order to guarantee an inclusive participation and then applied by means of two different surveys in living and extended care unit environments. Results permit to highlight that: (i) the four comfort domains show similar sensitivity trends, with acoustics having the greatest impact on people with autism spectrum disorder (ASD), while thermo-hygrometric, visual and IAQ sensitivity decreases as the stress scale increases; (ii) Severity of autism influenced the acoustic sensitivity, while age and the considered environment influenced thermo-hygrometric, visual and IAQ sensitivities. The proposed approach can be applied to well-being studies involving people with other types of conditions which could alter their perception of the built environment.

Three sub-adult chamois and two adult male roe deer were sighted in the Western Italian Alps while staying close to each other, without any interspecific interaction, near rocky outcrops with the characteristics of salt licks, likely of natural origin. This is apparently the first report of chamois and roe deer seen together at salt licks and suggests spatial overlap of two ungulates usually observed in different habitats. Their interspecific tolerance might be due to differences in their diets, which might, in turn, depend on overlooked local adaptations to coexist in the same habitat.

Summary: The tumor microenvironment is essential for mediating drug resistance and tumor progression. Here, we present a coculture system, which enables drug testing of colorectal cancer organoids and fibroblasts without additional matrix components such as Matrigel or basement membrane extracts. First, we describe steps to use a readout for high-throughput drug testing using a luminescence-based viability assay. Second, we detail a readout that uses flow cytometry to distinguish toxic effects on either colorectal cancer organoids or fibroblasts. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ObjectiveThe present study aims to understand the familial decision-making process on transport mode choice in adolescents with a focus on the parental perspective within this process.BackgroundActive travel contributes to adolescents’ overall physical activity and its positive health effects. Based on the social-learning theory, especially parents are assigned a central role for adolescents’ travel behavior. The aim of the present study was to examine how parents are involved in the decision-making process on transport mode choice in adolescents.MethodThe study is part of the cross-sectional mixed-methods ARRIVE study which includes semi-structured interviews with mothers (n = 12) and fathers (n = 7) of 11- to 14-year-old German adolescents. The interviews focused on travel behavior in adolescents and the decision-making process on transport mode choice from the parental perspective. All interviews were analyzed inductively using Thematic Analysis.ResultsOur study revealed that parents do not primarily decide for or against active travel in adolescents, but are mostly involved in the decision-making process, especially in case of a deviation from the main transport mode. Different forms of parental involvement in the decision-making process were identified. Some parents acted as main decision makers which is the highest form of involvement while others gave their children complete freedom of choose a transport mode for themselves. These parents accepted their child’s choice fully which shows a low involvement in the decision-making process.ConclusionThe results provide a deeper understanding of the familial decision-making process on travel behavior in adolescents. The results indicate an occasionally parental involvement in the decision-making process on the mainly used transport mode by adolescents, and that mothers and fathers are always involved when deviating from the main mode.ImplicationsFurther research should investigate changes in travel behavior from childhood to young adulthood to understand long-term travel decisions in families. Due to the findings that parents are often involved in the decision-making process on transport mode choice and that they mainly reported safety concerns as barriers to their children’s active travel, further research should focus especially on the social and physical environment of adolescents.

BackgroundThe relative contribution of changes in the cerebral white matter (WM) and cortical gray matter (GM) to the transition to dementia in patients with mild cognitive impairment (MCI) is not yet established. In this longitudinal study, we aimed to analyze MRI features that may predict the transition to dementia in patients with MCI and T2 hyperintensities in the cerebral WM, also known as leukoaraiosis.MethodsSixty-four participants with MCI and moderate to severe leukoaraiosis underwent baseline MRI examinations and annual neuropsychological testing over a 2 year period. The diagnosis of dementia was based on established criteria. We evaluated demographic, neuropsychological, and several MRI features at baseline as predictors of the clinical transition. The MRI features included visually assessed MRI features, such as the number of lacunes, microbleeds, and dilated perivascular spaces, and quantitative MRI features, such as volumes of the cortical GM, hippocampus, T2 hyperintensities, and diffusion indices of the cerebral WM. Additionally, we examined advanced quantitative features such as the fractal dimension (FD) of cortical GM and WM, which represents an index of tissue structural complexity derived from 3D-T1 weighted images. To assess the prediction of transition to dementia, we employed an XGBoost-based machine learning system using SHapley Additive exPlanations (SHAP) values to provide explainability to the machine learning model.ResultsAfter 2 years, 18 (28.1%) participants had transitioned from MCI to dementia. The area under the receiving operator characteristic curve was 0.69 (0.53, 0.85) [mean (90% confidence interval)]. The cortical GM-FD emerged as the top-ranking predictive feature of transition. Furthermore, aggregated quantitative neuroimaging features outperformed visually assessed MRI features in predicting conversion to dementia.DiscussionOur findings confirm the complementary roles of cortical GM and WM changes as underlying factors in the development of dementia in subjects with MCI and leukoaraiosis. FD appears to be a biomarker potentially more sensitive than other brain features.

IntroductionWhile there are several approaches to collect basic information on physical activity (PA) promotion policies, some governments require more in-depth overviews on the situation in their country. In Germany, the Federal Ministry of Health expressed its interest in collecting detailed data on target group specific PA promotion, as relevant competences are distributed across a wide range of political levels and sectors. This study describes the development of a policy brief on physical activity promotion for children and adolescents in Germany. In particular, it addresses two major gaps in the current literature by systematically assessing good practice examples and “routine practices,” i.e., PA promotion activities already taking place on large scale and regular basis.Materials and methodsBased on relevant national and international guidelines, the TARGET:PA tool was co-produced by researchers and ministry officials. It includes (1) PA recommendations, (2) national prevalence rates, (3) recommendations for PA promotion, and data on national (4) routine practices, (5) good practice projects and (6) policies. Data were collected for children and adolescents in Germany using desk research, semi-structured interviews and secondary data analysis.ResultsA policy brief and scientific background document were developed. Results showed that 46% of the 4–5-year-olds fulfil WHO recommendations but only 15% of the 11–17-year-olds, and that girls are less active than boys. Currently, in Germany no valid data are available on the PA behaviour of children under the age of three. An overview of routine practices for PA promotion for children and adolescents was compiled, and experts were asked to critically assess their effectiveness, reach and durability. Overall, 339 target group specific projects for PA promotion were found, with 22 classified as examples of good practice. National PA policies for children and adolescents were identified across different sectors and settings.ConclusionThe study provides a comprehensive overview of the current status of PA promotion for children and adolescents in Germany. The co-production of the policy brief was a strength of the study, as it allowed researchers to take the needs of ministry officials into account, and as it supported the immediate uptake of results in the policymaking process. Future studies should test the applicability of the TARGET:PA tool to different target groups and countries.

Understanding the immune system's foreign body response (FBR) is essential when developing and validating a biomaterial. Macrophage activation and proliferation are critical events in FBR that can determine the material's biocompatibility and fate in vivo. In this study, two different macro-encapsulation pouches intended for pancreatic islet transplantation were implanted into streptozotocin-induced diabetes rat models for 15 days. Post-explantation, the fibrotic capsules were analyzed by standard immunohistochemistry as well as non-invasive Raman microspectroscopy to determine the degree of FBR induced by both materials. The potential of Raman microspectroscopy to discern different processes of FBR was investigated and it was shown that Raman microspectroscopy is capable of targeting ECM components of the fibrotic capsule as well as pro and anti-inflammatory macrophage activation states, in a molecular-sensitive and marker-independent manner. In combination with multivariate analysis, spectral shifts reflecting conformational differences in Col I were identified and allowed to discriminate fibrotic and native interstitial connective tissue fibers. Moreover, spectral signatures retrieved from nuclei demonstrated changes in methylation states of nucleic acids in M1 and M2 phenotypes, relevant as indicator for fibrosis progression. This study could successfully implement Raman microspectroscopy as complementary tool to study in vivo immune-compatibility providing insightful information of FBR of biomaterials and medical devices, post-implantation.

IntroductionIdiopathic normal pressure hydrocephalus (INPH) is a neurological disorder that is potentially reversible and clinically characterized by a specific triad of symptoms, including gait disturbance, cognitive disorders, and urinary incontinence. In INPH assessment, the most commonly used test is the Timed Up and Go test (TUG), but a more comprehensive assessment would be necessary. The first aim of the present study is to verify the sensitivity of a protocol with both clinical and instrumental outcome measures for gait and balance in recognizing INPH patients. The second aim is to verify the most important spatio-temporal parameters in INPH assessment and their possible correlations with clinical outcome measures.MethodsBetween January 2019 and June 2022, we evaluated 70 INPH subjects. We assessed balance performances with the Berg Balance Scale (BBS), Short Physical Performance Battery (SPPB), and TUG, both single (ST) and dual task (DT). We also performed an instrumental gait assessment with the GAITRite electronic walkway system, asking the patients to walk on the carpet for one minute at normal speed, fast speed, and while performing a dual task. We compared the results with those of 20 age-matched healthy subjects (HS).ResultsINPH patients obtained statistically significant lower scores at the BBS, SPPB, and TUG DT but not at the TUG ST, likely because the DT involves cognitive factors altered in these subjects. Concerning instrumental gait evaluation, we found significant differences between HS and INPH patients in almost all spatio-temporal parameters except cadence, which is considered a relevant factor in INPH guidelines. We also found significant correlations between balance outcome measures and gait parameters.DiscussionOur results confirm the usefulness of BBS and suggest improving the assessment with SPPB. Although the TUG ST is the most commonly used test in the literature to evaluate INPH performances, it does not identify INPH; the TUG DT, instead, might be more useful. The GAITRite system is recognized as a quick and reliable tool to assess walking abilities and spatio-temporal parameters in INPH patients, and the most useful parameters are stride length, stride width, speed, and the percentage of double support. Both clinical and instrumental evaluation may be useful in recognizing subjects at risk for falls.

BackgroundHemorrhagic shock (HS) is responsible for approximately 2 million deaths per year worldwide and is caused in 80% by polytrauma. These patients need a precise and quick diagnostic, which should be based on a combination of laboratory markers and radiological data. Extracellular vesicles (EVs) were described as potential new markers and mediators in trauma. The aim of the present study was to analyze, whether the surface epitopes of plasma-EVs reflect HS in polytraumatized patients and whether cell-specific EV subpopulations are useful diagnostic tools.Material and methodsPlasma samples from polytraumatized patients (ISS ≥16) with HS (n=10) and without (n=15), were collected at emergency room (ER) and 24h after trauma. Plasma-EVs were isolated via size exclusion chromatography and EV-concentrations were detected by Coomassie Plus (Bradford) Assay. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with healthy controls (n=10). To investigate the diagnostic and prognostic potential of EVs subpopulations, results were correlated with clinical outcome parameters documented in the electronical patients’ record.ResultsWe observed a significant reduction of the total amount of plasma EVs in polytrauma patients with HS, as compared to polytrauma patients without HS and healthy controls. We found significant reduction of CD42a+ and CD41b+ (platelet-derived) EVs in all polytrauma patients, as well as a reduction of CD29+ EVs compared to healthy volunteers (*p

The assessment of nanoparticle cytotoxicity is challenging due to the lack of customized and standardized guidelines for nanoparticle testing. Nanoparticles, with their unique properties, can interfere with biochemical test methods, so multiple tests are required to fully assess their cellular effects. For a more reliable and comprehensive assessment, it is therefore imperative to include methods in nanoparticle testing routines that are not affected by particles and allow for the efficient integration of additional molecular techniques into the workflow. Digital holographic microscopy (DHM), an interferometric variant of quantitative phase imaging (QPI), has been demonstrated as a promising method for the label-free assessment of the cytotoxic potential of nanoparticles. Due to minimal interactions with the sample, DHM allows for further downstream analyses. In this study, we investigated the capabilities of DHM in a multimodal approach to assess cytotoxicity by directly comparing DHM-detected effects on the same cell population with two downstream biochemical assays. Therefore, the dry mass increase in RAW 264.7 macrophages and NIH-3T3 fibroblast populations measured by quantitative DHM phase contrast after incubation with poly(alkyl cyanoacrylate) nanoparticles for 24 h was compared to the cytotoxic control digitonin, and cell culture medium control. Viability was then determined using a metabolic activity assay (WST-8). Moreover, to determine cell death, supernatants were analyzed for the release of the enzyme lactate dehydrogenase (LDH assay). In a comparative analysis, in which the average half-maximal effective concentration (EC50) of the nanocarriers on the cells was determined, DHM was more sensitive to the effect of the nanoparticles on the used cell lines compared to the biochemical assays.

In this review, the application of five commercially available aqueous-based binders including sodium carboxyl methyl cellulose (CMC), polyacrylic acid (PAA), polyvinyl alcohol (PVA), polyethylene oxide (PEO), and polyethyleneimine (PEI) as well as some representative custom (or purpose) synthesized functional binders used in lithium sulfur (Li-S) batteries is summarized based on the main evaluation criteria of cycling capacity, battery lifetime, and areal sulfur loading (and, consequently, energy density of the battery). CMC with SBR (styrene butadiene rubber) has been reported with promising results in highly loaded sulfur cathodes (>5 mg cm−2 sulfur loading). PVA and PEI were confirmed to provide an enhanced adsorption of lithium polysulfides due to the interaction with hydroxyl and amine groups. No competitive advantage in electrochemical performance was demonstrated through the use of PAA and PEO. Water-based binders modified with polysulfide-trapping functional groups have complex fabrication processes, which hinders their commercial application. In general, achieving a high capacity and long cycling stability for highly loaded sulfur cathodes using commercial aqueous-based binders remains a significant challenge. Additionally, the scalability of these reported sulfur cathodes, in terms of complexity, cost, and stable electrochemical cycling, should be evaluated through further battery testing, particularly targeting pouch cell performance.

Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human–human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising vesicular stomatitis virus (VSV)-based vaccine to advance the approach for emergency applications. We compared monovalent and bivalent VSV vectors containing the Ebola virus (EBOV), glycoprotein (GP), and ANDV glycoprotein precursor (GPC) for protective efficacy in pre-, peri- and post-exposure immunization by the intraperitoneal and intranasal routes. Inclusion of the EBOV GP was based on its favorable immune cell targeting and the strong innate responses elicited by the VSV-EBOV vaccine. Our data indicates no difference of ANDV GPC expressing VSV vectors in pre-exposure immunization independent of route, but a potential benefit of the bivalent VSVs following peri- and post-exposure intraperitoneal vaccination.