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    Physiological Response to the COVID-19 Vaccine: Insights From a Prospective, Randomized, Single-Blinded, Crossover Trial.

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    BACKGROUND Rapid development and implementation of vaccines constituted a crucial step in containing the COVID-19 pandemic. A comprehensive understanding of physiological responses to these vaccines is important to build trust in medicine. OBJECTIVE This study aims to investigate temporal dynamics before and after COVID-19 vaccination in 4 physiological parameters as well as the duration of menstrual cycle phases. METHODS In a prospective trial, 17,825 adults in the Netherlands wore a medical device on their wrist for up to 9 months. The device recorded their physiological signals and synchronized with a complementary smartphone app. By means of multilevel quadratic regression, we examined changes in wearable-recorded breathing rate, wrist skin temperature, heart rate, heart rate variability, and objectively assessed the duration of menstrual cycle phases in menstruating participants to assess the effects of COVID-19 vaccination. RESULTS The recorded physiological signals demonstrated short-term increases in breathing rate and heart rate after COVID-19 vaccination followed by a prompt rebound to baseline levels likely reflecting biological mechanisms accompanying the immune response to vaccination. No sex differences were evident in the measured physiological responses. In menstruating participants, we found a 0.8% decrease in the duration of the menstrual phase following vaccination. CONCLUSIONS The observed short-term changes suggest that COVID-19 vaccines are not associated with long-term biophysical issues. Taken together, our work provides valuable insights into continuous fluctuations of physiological responses to vaccination and highlights the importance of digital solutions in health care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR2-10.1186/s13063-021-05241-5

    Evaluating individualized treatment effect predictions: A model-based perspective on discrimination and calibration assessment.

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    In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their performance. In this paper, we aim to facilitate the validation of prediction models for individualized treatment effects. The estimands of interest are defined based on the potential outcomes framework, which facilitates a comparison of existing and novel measures. In particular, we examine existing measures of discrimination for benefit (variations of the c-for-benefit), and propose model-based extensions to the treatment effect setting for discrimination and calibration metrics that have a strong basis in outcome risk prediction. The main focus is on randomized trial data with binary endpoints and on models that provide individualized treatment effect predictions and potential outcome predictions. We use simulated data to provide insight into the characteristics of the examined discrimination and calibration statistics under consideration, and further illustrate all methods in a trial of acute ischemic stroke treatment. The results show that the proposed model-based statistics had the best characteristics in terms of bias and accuracy. While resampling methods adjusted for the optimism of performance estimates in the development data, they had a high variance across replications that limited their accuracy. Therefore, individualized treatment effect models are best validated in independent data. To aid implementation, a software implementation of the proposed methods was made available in R

    Advancements in facial implantology: a review of hydroxyapatite applications and outcomes.

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    BACKGROUND The search for an ideal bone substitute in reconstructive surgery has led to the exploration of various materials, with hydroxyapatite (HaP) emerging as a promising candidate due to its biocompatibility, osteoconductive properties, and structural similarity to human bone. Despite its potential, there is a paucity of data on the long-term safety and efficacy of HaP in facial skeletal reconstruction and augmentation. METHODS We conducted a systematic review following PRISMA 2020 guidelines, searching PubMed/MEDLINE, Google Scholar, CENTRAL, and Web of Science databases for studies on hydroxyapatite facial implants in reconstruction and augmentation. RESULTS Our search yielded 12 studies that met our inclusion criteria, encompassing 74 patients treated with HaP implants for various indications including facial fractures/defects, aesthetic facial balancing, and after tumor resection. The studies reported on outcomes such as implant integration, complications, aesthetic results, and patient satisfaction, with a general trend indicating positive outcomes for the use of HaP in facial reconstruction. CONCLUSION Hydroxyapatite appears to be a viable and effective material for facial skeletal reconstruction and augmentation, offering benefits in terms of biocompatibility, osteoconductivity, and patient outcomes. However, limitations such as low mechanical strength and the need for further research on long-term safety and efficacy were identified. This review underscores the potential of HaP in craniofacial surgery while highlighting areas for future investigation

    Optimization of chemotherapy regimens using mathematical programming

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    From manual work to artificial intelligence: developments in data literacy and research infrastructure using the example of the Repertorium Academicum Germanicum (2001-2024).

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    The Repertorium Academicum Germanicum (RAG) is a digital research project on scholars in the Middle Ages and their impact on society in pre-modern Europe (1250-1550). The RAG database contains around 62,000 scholars with 400,000 life points located at 26,000 locations. The data is based on the university registers. The registers usually contain the names and places of origin of the students as well as the date of enrolment. This initial data is enriched in the research database with biographical data on subjects studied, professional activities and written works. The aim of the project is to create a knowledge-based prosopographic basis for research on the impact of scholars in premodern Europe

    Spontaneous duodenocutaneous fistula: a rare presentation of perforated duodenal ulcer.

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    OBJECTIVES Fistula formation between the duodenum and the skin of the anterior abdominal wall is a rare complication and reported most often following surgery. To the best of our knowledge, the development of a spontaneous duodenocutaneous fistula in association with duodenal ulcer has only been reported once. CASE PRESENTATION A 52-year-old female patient presented at the emergency department with a painful ulcer and erythema on the right abdominal wall. On admission, she was in extremely poor general and nutritional condition. Laboratory analysis revealed inflammation. An empiric antibiotic therapy was initiated; parenteral nutrition, fluid, and electrolyte resuscitation were started. An enterocutaneous fistula was postulated and confirmed by endoscopy identifying a perforated duodenal ulcer. Surgery was not a valuable option and a Foley catheter was inserted through the fistula. During further endoscopic interventions, the Foley catheter was first replaced by a jejunal tube and later by a percutaneous endoscopic gastrostomy with a jejunal limb for enteral nutrition. The fistula output decreased, the local infection was controlled and the nutritional status improved. CONCLUSIONS Three months later the fistula was closed and the gastrostomy tube was removed. After 2 years the patient was in good general and nutritional condition

    Pilot multicenter study to determine the utility of point-of-care ultrasound to predict difficulty of tracheal intubation using videolaryngoscopy with the McGrath™ Mac videolaryngoscope.

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    BACKGROUND Clinical airway screening tests used to predict difficulties during airway management have low sensitivity and specificity. Point-of-care airway ultrasound has described measurements related to problems with difficult direct laryngoscopy. Nevertheless, the correlation between ultrasound parameters and videolaryngoscopy has not been published yet. The aim of this multicenter, prospective observational pilot study was to evaluate the applicability of clinical parameters and ultrasound measurements to find potential tracheal intubation difficulties when videolaryngoscopy is used. METHODS Preoperatively, six clinical airway assessments were performed: (1) modified Mallampati score, (2) thyromental distance, (3) sternomental distance, (4) interincisal distance, (5) upper lip bite test, and (6) neck circumference. Six ultrasound parameters were measured in awake patients: (1) distance from skin to hyoid bone, (2) distance from skin to epiglottis, (3) hyomental distance in neutral head position, (4) hyomental distance in head-extended position, (5) distance from skin to the deepest part of the palate, and (6) sagittal tongue area. And finally, there was one ultrasound measure obtained in anesthetized patients, the compressed sagittal tongue area during videolaryngoscopy. The difficulty for tracheal intubation using a McGrath™ Mac videolaryngoscope, the percentage of glottic opening, and Cormack-Lehane grade were also assessed. RESULTS In this cohort of 119 subjects, tongue dimensions, particularly the sagittal tongue area, showed a robust association with increased intubation difficulty using videolaryngoscopy. A multiparametric model combining the following three ultrasound variables in awake patients: (a) the distance from skin to epiglottis, (b) the distance from skin to the deepest part of the palate, and (c) the sagittal tongue area, yielded a sensitivity of 92.3%, specificity of 94.5%, positive predictive value of 82.8%, and negative predictive value of 97.8% (p < 0.001). CONCLUSION Point-of-care airway ultrasound emerges as a more useful tool compared to traditional clinical scales to anticipate possible challenges during videolaryngoscopic intubation

    AI-driven Discovery of Morphomolecular Signatures in Toxicology.

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    Early identification of drug toxicity is essential yet challenging in drug development. At the preclinical stage, toxicity is assessed with histopathological examination of tissue sections from animal models to detect morphological lesions. To complement this analysis, toxicogenomics is increasingly employed to understand the mechanism of action of the compound and ultimately identify lesion-specific safety biomarkers for which in vitro assays can be designed. However, existing works that aim to identify morphological correlates of expression changes rely on qualitative or semi-quantitative morphological characterization and remain limited in scale or morphological diversity. Artificial intelligence (AI) offers a promising approach for quantitatively modeling this relationship at an unprecedented scale. Here, we introduce GEESE, an AI model designed to impute morphomolecular signatures in toxicology data. Our model was trained to predict 1,536 gene targets on a cohort of 8,231 hematoxylin and eosin-stained liver sections from Rattus norvegicus across 127 preclinical toxicity studies. The model, evaluated on 2,002 tissue sections from 29 held-out studies, can yield pseudo-spatially resolved gene expression maps, which we correlate with six key drug-induced liver injuries (DILI). From the resulting 25 million lesion-expression pairs, we established quantitative relations between up and downregulated genes and lesions. Validation of these signatures against toxicogenomic databases, pathway enrichment analyses, and human hepatocyte cell lines asserted their relevance. Overall, our study introduces new methods for characterizing toxicity at an unprecedented scale and granularity, paving the way for AI-driven discovery of toxicity biomarkers

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