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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 Liquid biomarkers are essential in trauma cases and critical care and offer valuable insights into the extent of injury, prognostic predictions, and treatment guidance. They can help assess the severity of organ damage (OD), assist in treatment decisions and forecast patient outcomes. Notably, small extracellular vesicles, particularly those involved in splenic trauma, have been overlooked. Here, we reanalyzed our data and explored whether monocyte-derived small EVs are correlated with AAST score (American Association for the Surgery of Trauma) scoring and are sensitive enough to distinguish the severity of splenic trauma in our explorative study. There was a correlation between monocyte-derived small extracellular vesicles (EVs) and the AAST score (rSp = 0.82, p

The Morris Water Maze (MWM) is the most commonly used assay for evaluating learning and memory in laboratory mice. Despite its widespread use, contemporary reviews have highlighted substantial methodological variation in experimental protocols and that the associated testing procedures are acutely (each trial) and chronically (testing across days) stressful; stress impairs attention, memory consolidation and the retrieval of learned information. Moreover, the interpretation of behavior within the MWM is often difficult because of wall hugging, non-spatial swim strategies, floating, and jumping off the escape platform. Together, these issues may compromise the reproducibility, generalizability, and predictability of experimental results, as well as animal welfare. To address these issues, and as an initial proof-of-principle, we first narrowed the spatial dimensions of the MWM by using a T-insert, which constrained and reduced the overall length of time/distance that the animal must swim in order to navigate to the escape platform, thus reducing stress and off-task behavior. Given the robust performance observed across spatial acquisition (learning and memory) as well as during reversal learning (executive function), we further reduced (by 43%) the overall distance and time that the animal must swim in order to find the escape platform in a bespoke standalone Water T-Maze (WTM). We show, across five experiments, procedural refinements to our protocol and demonstrate robust, reliable and reproducible indicators of learning, memory and executive functioning in a task that is also significantly more efficient (3 days of testing within the WTM vs. 11 days of testing within the MWM). Taken together, our WTM apparatus and protocol are a significant improvement over other water-based apparatuses and protocols for evaluating learning, memory, and executive functioning in laboratory mice.

Human noroviruses (HuNoVs) are a major cause of diarrheal disease, yet critical aspects of their biology, including cellular tropism, remain unclear. Although research has traditionally focused on the intestinal epithelium, the hypothesis that HuNoV infects macrophages has been recurrently discussed and is investigated here using a zebrafish larval model. Through single-cell RNA sequencing of dissected zebrafish intestines, we unbiasedly identified macrophages as host cells for HuNoV replication, with all three open reading frames mapped to individual macrophages. Notably, HuNoV preferentially infects actively phagocytosing inflammatory macrophages. HuNoV capsid proteins and double-stranded RNA colocalized within intestinal macrophages of infected zebrafish larvae, and the negative-strand RNA intermediate was detected within FACS-sorted macrophages. Flow cytometry confirmed viral replication within these macrophages, constituting approximately 23% of HuNoV’s host cells. Identifying macrophages as host cells prompts a reevaluation of their role in HuNoV pathogenesis, offering new directions for understanding and controlling this infection.

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.

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.

Background: Accurate longitudinal risk prediction for DCI (delayed cerebral ischemia) occurrence after subarachnoid hemorrhage (SAH) is essential for clinicians to administer appropriate and timely diagnostics, thereby improving treatment planning and outcome. This study aimed to develop an improved longitudinal DCI prediction model and evaluate its performance in predicting DCI between day 4 and 14 after aneurysm rupture. Methods: Two DCI classification models were trained: (1) a static model based on routinely collected demographics and SAH grading scores and (2) a dynamic model based on results from laboratory and blood gas analysis anchored at the time of DCI. A combined model was derived from these two using a voting approach. Multiple classifiers, including Logistic Regression, Support Vector Machines, Random Forests, Histogram-based Gradient Boosting, and Extremely Randomized Trees, were evaluated through cross-validation using anchored data. A leave-one-out simulation was then performed on the best-performing models to evaluate their longitudinal performance using time-dependent Receiver Operating Characteristic (ROC) analysis. Results: The training dataset included 218 patients, with 89 of them developing DCI (41%). In the anchored ROC analysis, the combined model achieved a ROC AUC of 0.73 ± 0.05 in predicting DCI onset, the static and the dynamic model achieved a ROC AUC of 0.69 ± 0.08 and 0.66 ± 0.08, respectively. In the leave-one-out simulation experiments, the dynamic and voting model showed a highly dynamic risk score (intra-patient score range was 0.25 [0.24, 0.49] and 0.17 [0.12, 0.25] for the dynamic and the voting model, respectively, for DCI occurrence over the course of disease. In the time-dependent ROC analysis, the dynamic model performed best until day 5.4, and afterwards the voting model showed the best performance. Conclusions: A machine learning model for longitudinal DCI risk assessment was developed comprising a static and a dynamic sub-model. The longitudinal performance evaluation highlighted substantial time dependence in model performance, underscoring the need for a longitudinal assessment of prediction models in intensive care settings. Moreover, clinicians need to be aware of these performance variations when performing a risk assessment and weight the different model outputs correspondingly.

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.

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

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.

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.