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Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Abstract Philips Visual Patient Avatar is an innovative approach to patient monitoring. Computer-based simulation studies have shown that it can improve diagnostic accuracy and confidence while reducing perceived workload. Following its integration into clinical practice, we conducted a single-centre qualitative study at the University Hospital Zurich to explore the views of anaesthesia, post-anaesthesia and intensive care providers on their experience with the technology. We used an online survey to assess its contributions in different clinical situations. We analysed the data thematically to identify key themes. Of the 510 healthcare providers contacted, 131 (25.7%) completed the survey and 154 comments were collected. Key themes included the detection of specific vital sign changes, focusing on temperature and oxygen saturation (41.9%, 34/81 comments in the operating room; 38.6%, 17/44 comments in the intensive care unit; 10.3%, 3/29 comments in the post-anaesthesia care unit). Additionally, the technology was perceived to support daily routines and situational awareness (28.4%, 23/81 comments in the OR; 9.1%, 4/44 comments in the ICU; 10.3%, 3/29 comments in the PACU). The study provides early, but strong evidence that the Philips Visual Patient Avatar assists healthcare providers in specific clinical situations in the perioperative and critical care settings.

Abstract Meningiomas are the most common primary intracranial tumors and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on brain MRI for diagnosis, treatment planning, and longitudinal treatment monitoring. However, automated, objective, and quantitative tools for non-invasive assessment of meningiomas on multi-sequence MR images are not available. Here we present the BraTS Pre-operative Meningioma Dataset, as the largest multi-institutional expert annotated multilabel meningioma multi-sequence MR image dataset to date. This dataset includes 1,141 multi-sequence MR images from six sites, each with four structural MRI sequences (T2-, T2/FLAIR-, pre-contrast T1-, and post-contrast T1-weighted) accompanied by expert manually refined segmentations of three distinct meningioma sub-compartments: enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Basic demographic data are provided including age at time of initial imaging, sex, and CNS WHO grade. The goal of releasing this dataset is to facilitate the development of automated computational methods for meningioma segmentation and expedite their incorporation into clinical practice, ultimately targeting improvement in the care of meningioma patients.

Abstract Spectrum power analysis in the low frequency oscillations (LFO) region of functional near infrared spectroscopy (fNIRS) is a promising method to deliver information about brain activation and therefore might be used for prognostication in patients with disorders of consciousness in the neurocritical care unit alongside with established methods. In this study, we measure the cortical hemodynamic response measured by fNIRS in the LFO region following auditory and somatosensory stimulation in healthy subjects. The significant hemodynamic reaction in the contralateral hemisphere correlation with the physiologic electric response suggests neurovascular coupling. In addition, we investigate power spectrum changes in steady state measurements of cerebral death patients and healthy subjects in the LFO region, the frequency of the heartbeat and respiration. The spectral power within the LFO region was lower in the patients with cerebral death compared to the healthy subjects, whereas there were no differences in spectral power for physiological activities such as heartbeat and respiration rate. This finding indicates the cerebral origin of our low frequency measurements. Therefore, LFO measurements are a potential method to detect brain activation in patients with disorders of consciousness and cerebral death. However, further studies in patients are needed to investigate its potential clinical use.

Abstract Despite significant progress in the medical field, there is still a pressing need for minimal‐invasive tools to assist with decision‐making, especially in cases of polytrauma. Our team explored the potential of serum‐derived large extracellular vesicles, so called microparticles/microvesicles/ectosomes, to serve as a supportive tool in decision‐making in polytrauma situations. We focused on whether monocyte derived large EVs may differentiate between polytrauma patients with internal organ injury (ISS > 15) and those without. Thus, we compared our EV data to soluble biomarkers such as tumour necrosis factor alpha (TNF alpha) and Interleukin‐8 (IL‐8). From the blood of 25 healthy and 26 patients with polytrauma large EVs were isolated, purified, and characterized. TNF alpha and IL‐8 levels were quantified. We found that levels of these monocyte derived large EVs were significantly higher in polytrauma patients with internal organ damage and correlated with the ISS. Interestingly, we also observed a decline in AnnV+CD14+ large EVs during normal recovery after trauma. Thus, inflammatory serological markers as TNF alpha and as IL‐8 demonstrated an inability to discriminate between polytrauma patients with or without internal organ damage, such as spleen, kidney, or liver lacerations/ruptures. However, TNF and IL‐8 levels were elevated in polytrauma cases overall when contrasted with healthy non‐traumatic controls. These findings suggest that delving deeper into the potential of AnnV+ large EVs derived from monocytes could highly beneficial in the managment of polytrauma, potentially surpassing the efficacy of commonly used serum markers.

Abstract The circadian clock is a molecular timekeeper, present from cyanobacteria to mammals, that coordinates internal physiology with the external environment. The clock has a 24-h period however development proceeds with its own timing, raising the question of how these interact. Using the intestine of Drosophila melanogaster as a model for organ development, we track how and when the circadian clock emerges in specific cell types. We find that the circadian clock begins abruptly in the adult intestine and gradually synchronizes to the environment after intestinal development is complete. This delayed start occurs because individual cells at earlier stages lack the complete circadian clock gene network. As the intestine develops, the circadian clock is first consolidated in intestinal stem cells with changes in Ecdysone and Hnf4 signalling influencing the transcriptional activity of Clk/cyc to drive the expression of tim, Pdp1, and vri. In the mature intestine, stem cell lineage commitment transiently disrupts clock activity in differentiating progeny, mirroring early developmental clock-less transitions. Our data show that clock function and differentiation are incompatible and provide a paradigm for studying circadian clocks in development and stem cell lineages.

In March 2020, at the onset of the coronavirus disease 2019 (COVID-19) pandemic in the United States, the Southern California Extracorporeal Membrane Oxygenation (ECMO) Consortium was formed. The consortium included physicians and coordinators from the 4 ECMO centers in San Diego County. Guidelines were created to ensure that ECMO was delivered equitably and in a resource effective manner across the county during the pandemic. A biomedical ethicist reviewed the guidelines to ensure ECMO use would provide maximal community benefit of this limited resource. The San Diego County Health and Human Services Agency further incorporated the guidelines into its plans for the allocation of scarce resources. The consortium held weekly video conferences to review countywide ECMO capacity (including census and staffing), share data, and discuss clinical practices and difficult cases. Equipment exchanges between ECMO centers maximized regional capacity. From March 1 to November 30, 2020, consortium participants placed 97 patients on ECMO. No eligible patients were denied ECMO due to lack of resources or capacity. The Southern California ECMO Consortium may serve as a model for other communities seeking to optimize ECMO resources during the current COVID-19 or future pandemics.

This case study examines the adaptation of an existing online, asynchronous faculty development resource at the University of New Mexico to support the unanticipated need for all instructors to teach remotely starting in spring 2020, due to the COVID-19 pandemic. The course--entitled Evidence-Based Practices for Teaching Online (EBPTO)--was previously utilized to support instructor transitions to distance education by applying constructivist principles to the development of evidence-based online teaching practices. The course was adapted to address institutional and instructor needs as a result of the pandemic, including increasing facilitation resources. The largest EBPTO cohort, with 117 participants, began in June 2020. Data were collected through a reflective journal administered at the mid-point and an end-of-course survey. Analysis of the reflective journal provided insight into participants' learning experience in terms of key "takeaways," LMS tools that they had the opportunity to practice, and "lingering questions" that they had. The top 3 takeaways were the usefulness of course mapping, the usefulness of backwards design, and the deepening familiarity with LMS tools. Results from the end-of-course survey showed positive feedback from participants regarding perceived achievement of the course learning objectives, even after scaling the course to accommodate the large number of instructors moving to remote instruction.

Purpose: To evaluate how the crown-to-implant (C/I) ratio affects the loss of crestal bone at single-crown implants and bridges in patients with periodontal disease. Materials and Methods: A total of 39 patients treated for periodontitis were rehabilitated with 108 implant-supported single crowns and bridges. Each patient was examined over a 5- to 20-year period on a 3- to 6-month recall schedule. At each session, we recorded periodontal clinical parameters. In addition, intraoral radiographs were taken after superstructure insertion (baseline) and then at 1, 3, 5, 10, 15, and 20 years. The study population was divided by anatomical C/I ratio (Group 1: C/I = 1, Group 2: C/I > 1). Results: Implants had a 96.2% 5-year survival rate and 92.6% 20-year survival rate. The overall prevalence was 10.1% for mucositis and 1.1% for peri-implantitis. The survival rate (P = .68), incidence of mucositis (P = .325), and incidence of peri-implantitis (P = .077) did not significantly differ in the group comparison. The mean annual peri-implant bone loss was 0.09 ± 0.41 mm and was not significantly different between the groups. Mean bone loss was not significantly different until the 10th year of observation, during which Group 2 presented significantly less bone loss. The correlation of annual bone loss and clinical C/I ratio showed a small but significant negative effect throughout the entire study period (R = -0.217; P < .01). Conclusions: Increased crestal bone loss was not observed with implants with higher C/I ratios, both anatomical and clinical, and they even showed signs of less crestal bone loss. [ABSTRACT FROM AUTHOR]

Delayed cerebral ischemia (DCI) occurs in up to one third of patients suffering from aneurysmal subarachnoid hemorrhage (aSAH). Untreated, it leads to secondary cerebral infarctions and is frequently associated with death or severe disability. After aneurysm rupture, erythrocytes in the subarachnoid space lyse and liberate free hemoglobin (Hb), a key driver for the development of DCI. Hemoglobin in the cerebrospinal fluid (CSF-Hb) can be analyzed through a two-step procedure of centrifugation to exclude intact erythrocytes and subsequent spectrophotometric quantification. This analysis can only be done in specialized laboratories but not at the bedside in the intensive care unit. This limits the number of tests done, increases the variability of the results and restricts accuracy. Bedside measurements of CSF-Hb as a biomarker with a point of care diagnostic test system would allow for a continuous monitoring for the risk of DCI in the individual patient. In this study, a microfluidic chip was explored that allows to continuously separate blood particles from CSF or plasma based on acoustophoresis. An in vitro test bench was developed to test in-line measurements with the developed microfluidic chip and a spectrometer. The proof of principle for a continuous particle separation device has been established with diluted blood and CSF samples from animals and aSAH patients, respectively. Processing 1 mL of blood in our microfluidic device was achieved within around 70 min demonstrating only minor deviations from the gold standard centrifugation (7% average error of patient samples), while saving several hours of processing time and additionally the reduction of deviations in the results due to manual labor.

Introduction An increasing number of tracheotomised and/or ventilated patients with high-cost out-of-hospital intensive care needs and, at the same time, a decreasing number of healthcare professionals inevitably lead to challenges in the care of this patient population. In addition, little is known about this population, their health restrictions, needs, patient journeys, care structures and processes. The project ‘Needs, requirements and cross-sectoral care pathways of out-of-hospital ventilated intensive care patients’ (ATME) aims to analyse these aspects and explore current care structures to inform further development of care in line with patients’ needs and requirements.Methods and analysis Qualitative and quantitative methods will be used. In preparation of a semistandardised survey, exploratory interviews will be conducted with tracheotomised and/or ventilated patients with out-of-hospital intensive care needs (TVPOI) (n=15), nursing care providers (n=30), outpatient medical centres, as well as outpatient medical, medical technology and therapeutic care providers (n=35). Three semistandardised survey questionnaires for TVPOI (n=2,000) will be developed and conducted with nursing care facilities (n=250) and outpatient medical centres for mechanical ventilation (n=25). Content analyses will be conducted for qualitative data; survey data will be analysed descriptively. In addition, healthcare claims data will be analysed descriptively to provide information on patient journeys. Three result workshops and one consensus conference will be carried out with representatives of the relevant target groups to analyse the suitability of care structures and to develop recommendations for action to improve TVPOI.Ethics and dissemination The ATME study received a positive vote from the Ethics Committee of the Osnabrück University of Applied Sciences and is registered in ‘Deutsches Register Klinischer Studien (DRKS)’ (registration number: DRKS00030891). The study results will be presented at national conferences and in relevant peer-reviewed journals. Additionally, study results will be published by the funding institution (the Innovation Committee of the Federal Joint Committee) on their website.

Pigs can be an important model for preclinical biological research, including neurological diseases such as Alcohol Use Disorder. Such research often involves longitudinal assessment of changes in motor coordination as the disease or disorder progresses. Current motor coordination tests in pigs are derived from behavioral assessments in rodents and lack critical aspects of face and construct validity. While such tests may permit for the comparison of experimental results to rodents, a lack of validation studies of such tests in the pig itself may preclude the drawing of meaningful conclusions. To address this knowledge gap, an apparatus modeled after a horizontally placed ladder and where the height of the rungs could be adjusted was developed. The protocol that was employed within the apparatus mimicked the walk and turn test of the human standardized field sobriety test. Here, five Sinclair miniature pigs were trained to cross the horizontally placed ladder, starting at a rung height of six inches and decreasing to three inches in one-inch increments. It was demonstrated that pigs can reliably learn to cross the ladder, with few errors, under baseline/unimpaired conditions. These animals were then involved in a voluntary consumption of ethanol study where animals were longitudinally evaluated for motor coordination changes at baseline, 2.5, 5, 7.5, and 10% ethanol concentrations subsequently to consuming ethanol. Consistent with our predictions, relative to baseline performance, motor incoordination increased as voluntary consumption of escalating concentrations of ethanol increased. Together these data highlight that the horizontal ladder test (HLT) test protocol is a novel, optimized and reliable test for evaluating motor coordination as well as changes in motor coordination in pigs.

Background:. The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. Methods:. Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. Results:. Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p

BackgroundAchieving physical activity (PA) guidelines’ recommendation of 150 minutes of moderate-to-vigorous PA per week has been shown to reduce the risk of many chronic conditions. Despite the overwhelming evidence in this field, PA levels remain low globally. By creating engaging mobile health (mHealth) interventions through strategies such as just-in-time adaptive interventions (JITAIs) that are tailored to an individual’s dynamic state, there is potential to increase PA levels. However, generating personalized content can take a long time due to various versions of content required for the personalization algorithms. ChatGPT presents an incredible opportunity to rapidly produce tailored content; however, there is a lack of studies exploring its feasibility. ObjectiveThis study aimed to (1) explore the feasibility of using ChatGPT to create content for a PA JITAI mobile app and (2) describe lessons learned and future recommendations for using ChatGPT in the development of mHealth JITAI content. MethodsDuring phase 1, we used Pathverse, a no-code app builder, and ChatGPT to develop a JITAI app to help parents support their child’s PA levels. The intervention was developed based on the Multi-Process Action Control (M-PAC) framework, and the necessary behavior change techniques targeting the M-PAC constructs were implemented in the app design to help parents support their child’s PA. The acceptability of using ChatGPT for this purpose was discussed to determine its feasibility. In phase 2, we summarized the lessons we learned during the JITAI content development process using ChatGPT and generated recommendations to inform future similar use cases. ResultsIn phase 1, by using specific prompts, we efficiently generated content for 13 lessons relating to increasing parental support for their child’s PA following the M-PAC framework. It was determined that using ChatGPT for this case study to develop PA content for a JITAI was acceptable. In phase 2, we summarized our recommendations into the following six steps when using ChatGPT to create content for mHealth behavior interventions: (1) determine target behavior, (2) ground the intervention in behavior change theory, (3) design the intervention structure, (4) input intervention structure and behavior change constructs into ChatGPT, (5) revise the ChatGPT response, and (6) customize the response to be used in the intervention. ConclusionsChatGPT offers a remarkable opportunity for rapid content creation in the context of an mHealth JITAI. Although our case study demonstrated that ChatGPT was acceptable, it is essential to approach its use, along with other language models, with caution. Before delivering content to population groups, expert review is crucial to ensure accuracy and relevancy. Future research and application of these guidelines are imperative as we deepen our understanding of ChatGPT and its interactions with human input.

Abstract Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell–cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co‐isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins. In the pursuit of improved EV isolation techniques, we introduce multimodal flowthrough chromatography (MFC) as a scalable alternative to size exclusion chromatography (SEC). The use of MFC offers significant advantages for purifying EVs, resulting in enhanced yields and increased purity with respect to protein and nucleic acid co‐isolates from conditioned 3D cell culture media. Compared to SEC, significantly higher EV yields with similar purity and preserved functionality were also obtained with MFC in 2D cell cultures. Additionally, MFC yielded EVs from serum with comparable purity to SEC and similar apolipoprotein B content. Overall, MFC presents an advancement in EV purification yielding EVs with high recovery, purity, and functionality, and offers an accessible improvement to researchers currently employing SEC.