Journal: Frontiers in Medicine

Abbreviation

Front. Med.

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Frontiers Media

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ISSN

2296-858X

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2018 - 201952020 - 202419
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Publications 1 - 10 of 24
  • Triggering Postural Movements With Virtual Reality Technology in Healthy Young and Older Adults: A Cross-Sectional Validation Study for Early Dementia Screening
    Item type: Journal Article
    Imaoka, Yu; Saba, Nadja; Vanhoestenberghe, Anne; et al. (2020)
    Frontiers in Medicine
    With the ultimate aim of early diagnosis of dementia, a new body balance assessment system with integrated head-mounted display-based virtual reality (VR) has been developed. We hypothesized that people would sway more in anterior-posterior (AP) direction when they were exposed to a VR environment where we intentionally provoked movements in forward and backward directions. A total of 14 healthy older adults (OA) (73.14±4.26 years) and 15 healthy young adults (YA) (24.93±1.49 years) were assessed for group differences in sway behavior. Body sway speed in 22 different conditions with and without VR environments was analyzed. Significant differences and large effect sizes were observed in AP sway under the VR environments (OA with P < 0.02; effect size> 0.61, YA with P < 0.003; effect size> 0.72) compared to the baseline condition without the VR environments. In addition, significant differences were found between the two groups in AP sway in all test conditions (P < 0.01). Our study shows that a VR environment can trigger body sway in an expected direction, which may indicate that it is possible to enhance the sensitivity of balance assessment by integrating immersive VR environments. The result of this study warrants a cross-sectional study in which OA diagnosed with and without dementia are compared on their sway behavior.
  • A Pilot Observational Study Assessing Long-Term Changes in Clinical Parameters, Functional Capacity and Fall Risk of Patients With Chronic Renal Disease Scheduled for Hemodialysis
    Item type: Journal Article
    Zemp, Damiano D.; Giannini, Olivier; Quadri, Pierluigi; et al. (2022)
    Frontiers in Medicine
    Background: Patients with end-stage renal disease are known to be particularly frail, and the cause is still widely seen as being directly related to specific factors in renal replacement therapy. However, a closer examination of the transitional phase from predialysis to long-term hemodialysis leads to controversial explanations, considering that the frailty process is already well-described in the early stages of renal insufficiency. This study aims to describe longitudinally and multifactorially changes in the period extending from the decision to start the replacement therapy through to the end of 2 years of hemodialysis. We hypothesized that frailty is pre-existent in the predialysis phase and does not worsen with the beginning of the replacement therapy. Between 2015 and 2018 we recruited 25 patients (72.3 ± 5.7 years old) in a predialysis program, with the expectation that replacement therapy would begin within the coming few months. Methods: The patients underwent a baseline visit before starting hemodialysis, with 4 follow-up visits in the first 2 years of treatment. Health status, physical performance, cognitive functioning, hematology parameters, and adverse events were monitored during the study period. Results: At baseline, our sample had a high variability with patients ranging from extremely frail to very fit. In the 14 participants that did not drop out of the study, out of 32 clinical and functional measures, a statistically significant worsening was only observed in the Short Physical Performance Battery (SPPB) score (p < 0.01, F = 8.50) and the number of comorbidities (p = 0.01, F = 3.94). A careful analysis, however, reveals a quite stable situation in the first year of replacement therapy, for both frail and fit participants and a deterioration in the second year that in frail participants could lead to death. Conclusion: Our results should stimulate a reassessment about the role of a predialysis program in reducing complications during the transitional phase, but also about frailty prevention programs once hemodialysis has begun, for both frail and fit patients, to maintain satisfactory health status.
  • Early Prediction of Sepsis in the ICU Using Machine Learning: A Systematic Review
    Item type: Review Article
    Moor, Michael; Rieck, Bastian Alexander; Horn, Max; et al. (2021)
    Frontiers in Medicine
    Background: Sepsis is among the leading causes of death in intensive care units (ICUs) worldwide and its recognition, particularly in the early stages of the disease, remains a medical challenge. The advent of an affluence of available digital health data has created a setting in which machine learning can be used for digital biomarker discovery, with the ultimate goal to advance the early recognition of sepsis. Objective: To systematically review and evaluate studies employing machine learning for the prediction of sepsis in the ICU. Data Sources: Using Embase, Google Scholar, PubMed/Medline, Scopus, and Web of Science, we systematically searched the existing literature for machine learning-driven sepsis onset prediction for patients in the ICU. Study Eligibility Criteria: All peer-reviewed articles using machine learning for the prediction of sepsis onset in adult ICU patients were included. Studies focusing on patient populations outside the ICU were excluded. Study Appraisal and Synthesis Methods: A systematic review was performed according to the PRISMA guidelines. Moreover, a quality assessment of all eligible studies was performed. Results: Out of 974 identified articles, 22 and 21 met the criteria to be included in the systematic review and quality assessment, respectively. A multitude of machine learning algorithms were applied to refine the early prediction of sepsis. The quality of the studies ranged from “poor” (satisfying ≤ 40% of the quality criteria) to “very good” (satisfying ≥ 90% of the quality criteria). The majority of the studies (n = 19, 86.4%) employed an offline training scenario combined with a horizon evaluation, while two studies implemented an online scenario (n = 2, 9.1%). The massive inter-study heterogeneity in terms of model development, sepsis definition, prediction time windows, and outcomes precluded a meta-analysis. Last, only two studies provided publicly accessible source code and data sources fostering reproducibility. Limitations: Articles were only eligible for inclusion when employing machine learning algorithms for the prediction of sepsis onset in the ICU. This restriction led to the exclusion of studies focusing on the prediction of septic shock, sepsis-related mortality, and patient populations outside the ICU. Conclusions and Key Findings: A growing number of studies employs machine learning to optimize the early prediction of sepsis through digital biomarker discovery. This review, however, highlights several shortcomings of the current approaches, including low comparability and reproducibility. Finally, we gather recommendations how these challenges can be addressed before deploying these models in prospective analyses. Systematic Review Registration Number: CRD42020200133.
  • Prospective Design, Rapid Prototyping, and Testing of Smart Dressings, Drug Delivery Patches, and Replacement Body Parts Using Microscopy Aided Design and ManufacturE (MADAME)
    Item type: Journal Article
    Sidler, Hans-Jörg; Duvenage, Jacob; Anderson, Eric J.; et al. (2018)
    Frontiers in Medicine
    Natural materials exhibit smart properties including gradients in biophysical properties that engender higher order functions, as well as stimuli-responsive properties which integrate sensor and/or actuator capacities. Elucidation of mechanisms underpinning such smart material properties (i), and translation of that understanding (ii), represent two of the biggest challenges in emulating natural design paradigms for design and manufacture of disruptive materials, parts, and products. Microscopy Aided Design And ManufacturE (MADAME) stands for a computer-aided additive manufacturing platform that incorporates multidimensional (multi-D) printing and computer-controlled weaving. MADAME enables the creation of composite design motifs emulating e.g., patterns of woven protein fibers as well as gradients in different caliber porosities, mechanical, and molecular properties, found in natural tissues, from the skin on bones (periosteum) to tree bark. Insodoing, MADAME provides a means to manufacture a new genre of smart materials, products and replacement body parts that exhibit advantageous properties both under the influence of as well as harnessing dynamic mechanical loads to activate material properties (mechanoactive properties). This Technical Report introduces the MADAME technology platform and its associated machine-based workflow (pipeline), provides basic technical background of the novel technology and its applications, and discusses advantages and disadvantages of the approach in context of current 3 and 4D printing platforms.
  • Predicting risk for nocturnal hypoglycemia after physical activity in children with type 1 diabetes
    Item type: Journal Article
    Leutheuser, Heike; Bartholet, Marc; Marx, Alexander; et al. (2024)
    Frontiers in Medicine
    Children with type 1 diabetes (T1D) frequently have nocturnal hypoglycemia, daytime physical activity being the most important risk factor. The risk for late post-exercise hypoglycemia depends on various factors and is difficult to anticipate. The availability of continuous glucose monitoring (CGM) enabled the development of various machine learning approaches for nocturnal hypoglycemia prediction for different prediction horizons. Studies focusing on nocturnal hypoglycemia prediction in children are scarce, and none, to the best knowledge of the authors, investigate the effect of previous physical activity. The primary objective of this work was to assess the risk of hypoglycemia throughout the night (prediction horizon 9 h) associated with physical activity in children with T1D using data from a structured setting. Continuous glucose and physiological data from a sports day camp for children with T1D were input for logistic regression, random forest, and deep neural network models. Results were evaluated using the F2 score, adding more weight to misclassifications as false negatives. Data of 13 children (4 female, mean age 11.3 years) were analyzed. Nocturnal hypoglycemia occurred in 18 of a total included 66 nights. Random forest using only glucose data achieved a sensitivity of 71.1% and a specificity of 75.8% for nocturnal hypoglycemia prediction. Predicting the risk of nocturnal hypoglycemia for the upcoming night at bedtime is clinically highly relevant, as it allows appropriate actions to be taken-to lighten the burden for children with T1D and their families.
  • Production of Mass-Separated Erbium-169 Towards the First Preclinical in vitro Investigations
    Item type: Journal Article
    Talip, Zeynep; Borgna, Francesca; Müller, Cristina; et al. (2021)
    Frontiers in Medicine
    The β−-particle-emitting erbium-169 is a potential radionuclide toward therapy of metastasized cancer diseases. It can be produced in nuclear research reactors, irradiating isotopically-enriched 168Er2O3. This path, however, is not suitable for receptor-targeted radionuclide therapy, where high specific molar activities are required. In this study, an electromagnetic isotope separation technique was applied after neutron irradiation to boost the specific activity by separating 169Er from 168Er targets. The separation efficiency increased up to 0.5% using resonant laser ionization. A subsequent chemical purification process was developed as well as activity standardization of the radionuclidically pure 169Er. The quality of the 169Er product permitted radiolabeling and pre-clinical studies. A preliminary in vitro experiment was accomplished, using a 169Er-PSMA-617, to show the potential of 169Er to reduce tumor cell viability.
  • Sensitization of the Angiotensin II AT1 Receptor Contributes to RKIP-Induced Symptoms of Heart Failure
    Item type: Journal Article
    Wolf, Stefan; Abd Alla, Joshua; Quitterer, Ursula (2019)
    Frontiers in Medicine
    Inhibition of the G-protein-coupled receptor kinase 2 (GRK2) is an emerging treatment approach for heart failure. Therefore, cardio-protective mechanisms induced by GRK2 inhibition are under investigation. We compared two different GRK2 inhibitors, i.e., (i) the dual-specific GRK2 and raf kinase inhibitor protein, RKIP, and (ii) the dominant-negative GRK2-K220R mutant. We found that RKIP induced a strong sensitization of Gq/11-dependent, heart failure-promoting angiotensin II AT1 receptor signaling. The AT1-sensitizing function of RKIP was mediated by the RKIP-GRK2 interaction because the RKIP-S153V mutant, which does not interact with GRK2, had no effect on AT1-stimulated signaling. In contrast, GRK2-K220R significantly inhibited the AT1-stimulated signal. The in vivo relevance of these major differences between two different approaches of GRK2 inhibition was analyzed by generation of transgenic mice with myocardium-specific expression of RKIP and GRK2-K220R. Our results showed that a moderately increased cardiac protein level of RKIP was sufficient to induce major symptoms of heart failure in aged, 8-months-old RKIP-transgenic mice in two different genetic backgrounds. In contrast, GRK2-K220R protected against chronic pressure overload-induced cardiac dysfunction. The AT1 receptor contributed to RKIP-induced heart failure because treatment with the AT1 receptor antagonist, losartan, retarded symptoms of heart failure in RKIP-transgenic mice. Thus, sensitization of the heart failure-promoting AT1 receptor by the RKIP-GRK2 interaction contributes to heart failure whereas dominant-negative GRK2-K220R is cardioprotective. Because RKIP is up-regulated on cardiac biopsy specimens of heart failure patients, the deduced heart failure-promoting mechanism of RKIP could also be relevant for the human disease.
  • Effects of an In-home Multicomponent Exergame Training on Physical Functions, Cognition, and Brain Volume of Older Adults: A Randomized Controlled Trial
    Item type: Journal Article
    Adcock, Manuela; Fankhauser, Mélanie; Post, Jennifer; et al. (2020)
    Frontiers in Medicine
    Aging is associated with a decline in physical functions, cognition and brain structure. Considering that human life is based on an inseparable physical-cognitive interplay, combined physical-cognitive training through exergames is a promising approach to counteract age-related impairments. The aim of this study was to assess the effects of an in-home multicomponent exergame training on [i] physical and cognitive functions and [ii] brain volume of older adults compared to a usual care control group. Thirty-seven healthy and independently living older adults aged 65 years and older were randomly assigned to an intervention (exergame training) or a control (usual care) group. Over 16 weeks, the participants of the intervention group absolved three home-based exergame sessions per week (à 30–40 min) including Tai Chi-inspired exercises, dancing and step-based cognitive games. The control participants continued with their normal daily living. Pre- and post-measurements included assessments of physical (gait parameters, functional muscle strength, balance, aerobic endurance) and cognitive (processing speed, short-term attention span, working memory, inhibition, mental flexibility) functions. T1-weighted magnetic resonance imaging was conducted to assess brain volume. Thirty-one participants (mean age = 73.9 ± 6.4 years, range = 65–90 years, 16 female) completed the study. Inhibition and working memory significantly improved post-intervention in favor of the intervention group [inhibition: F(1) = 2.537, p = 0.046, n2p = 0.11, working memory: F(1) = 5.872, p = 0.015, n2p = 0.02]. Two measures of short-term attentional span showed improvements after training in favor of the control group [F(1) = 4.309, p = 0.038, n2p = 0.03, F(1) = 8.504, p = 0.004, n2p = 0.04]. No significant training effects were evident for physical functions or brain volume. Both groups exhibited a significant decrease in gray matter volume of frontal areas and the hippocampus over time. The findings indicate a positive influence of exergame training on executive functioning. No improvements in physical functions or brain volume were evident in this study. Better adapted individualized training challenge and a longer training period are suggested. Further studies are needed that assess training-related structural brain plasticity and its effect on performance, daily life functioning and healthy aging.
  • Effect of COVID-19 vaccination on the menstrual cycle
    Item type: Review Article
    Chao, Melissa Jung; Menon, Carlo; Elgendi, Mohamed (2022)
    Frontiers in Medicine
    Numerous anecdotal accounts and qualitative research studies have reported on post-vaccination menstrual irregularities in women of reproductive age. However, none have quantified the impact. This is the first systematic review and meta-analysis to quantify and characterize the menstrual irregularities associated with vaccination for women of reproductive age. A search on July 20, 2022, retrieved articles published between December 1, 2019, and July 1, 2022, from MEDLINE, Embase, and Web of Science. The included articles were studies with full texts written in English that reported on menstrual irregularities for vaccinated vs. unvaccinated women of reproductive age. The quality of the studies was evaluated using the Study Quality Assessment Tool for Observation Cohort and Cross-Sectional Studies. Four observational studies were included. Review Manager was used to generating a forest plot with odds ratios (ORs) at the 95% confidence interval (CI), finding statistically significant associations between vaccination and menstrual irregularities for 25,054 women of reproductive age (OR = 1.91, CI: 1.76–2.07) with a significant overall effect of the mean (Z = 16.01, p < 0.0001). The studies were heterogeneous with significant dispersion of values (χ2 = 195.10 at df = 3, p < 0.00001, I2 = 98%). The findings of this systematic review and meta-analysis are limited by the availability of quantitative data. The results have implications for treating women of reproductive age with menstrual irregularities and informing them about the potential side effects of vaccinations.
  • Discovery of Pathologic GPCR Aggregation
    Item type: Review Article
    Quitterer, Ursula; AbdAlla, Said (2019)
    Frontiers in Medicine
    The family of G-protein-coupled receptors (GPCRs) is one of the most important drug targets. Mechanisms underlying GPCR activation and signaling are therefore of great pharmacologic interest. It was long thought that GPCRs exist and function as monomers. This feature was considered to distinguish GPCRs from other membrane receptors such as receptor tyrosine kinases or cytokine receptors, which signal from dimeric receptor complexes. But during the last two decades it was increasingly recognized that GPCRs can undergo aggregation to form dimers and higher order oligomers, resulting in homomeric and/or heteromeric protein complexes with different stoichiometries. Moreover, this protein complex formation could modify GPCR signaling and function. We contributed to this paradigm shift in GPCR pharmacology by the discovery of the first pathologic GPCR aggregation, which is the protein complex formation between the angiotensin II AT1 receptor and the bradykinin B2 receptor. Increased AT1-B2 heteromerization accounts for the angiotensin II hypersensitivity of pregnant women with preeclampsia hypertension. Since the discovery of AT1-B2, other pathologic GPCR aggregates were found, which contribute to atherosclerosis, neurodegeneration and Alzheimer's disease. As a result of our findings, pathologic GPCR aggregation appears as an independent and disease-specific process, which is increasingly considered as a novel target for pharmacologic intervention.
Publications 1 - 10 of 24